Compounds of the formula ##STR1## where R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to C.sub.6 alkyl; C.sub.5 or C.sub.6 cycloalkyl; C.sub.5 or C.sub.6 cycloalkenyl; phenyl optionally substituted with a substitutent selected from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected from the group oxygen, nitrogen and sulfur; Y is the radical selected from (CH.sub.2).sub.n, (C.sub.4 H.sub.8 S), (C.sub.4 H.sub.8 O) and ##STR2## where R is hydrogen or C.sub.1 to C.sub.6 alkyl and n is the integer 4 or 5; and X is selected from the group methanesulfonate, benzenesulfonate, p-toluenesulfonate, nitrate, chloride, bromide and iodide. Methods for preparing these compounds are also disclosed. The compounds of the present invention are useful as anticholinergic agents.

FIELD OF THE INVENTION 
This invention relates to glycolic acid esters and pharmaceutically 
acceptable, non-toxic salts thereof and to methods for preparing these 
compounds. More particularly this invention relates to azoniaspiro 
glycolates, and to pharmaceutical compositions comprising one or more of 
the above compounds and to methods for achieving anticholinergic effects 
in mammals by using these compounds. 
In summary, the compounds in accordance with the present invention can be 
represented by the following generic formula 
##STR3## 
where R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to 
C.sub.6 alkyl; C.sub.5 or C.sub.6 cycloalkyl; C.sub.5 or C.sub.6 
cycloalkenyl; phenyl optionally substituted with a substitutent selected 
from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and 
halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected 
from the group oxygen, nitrogen and sulfur; Y is the radical selected from 
(CH.sub.2).sub.n, (C.sub.4 H.sub.8 S) and 
##STR4## 
where R is hydrogen or C.sub.1 to C.sub.6 alkyl and n is the integer 4 or 
5; and X is selected from the group methanesulfonate, benzenesulfonate, 
p-toluenesulfonate, nitrate, chloride, bromide and iodide. 
The process for preparing the compounds of the present invention of formula 
I comprises treating a compound of the formula 
##STR5## 
with Z--Y--Z, where Z are the groups methanesulfonyl, benzenesulfonyl, 
p-toluenesulfonyl, chloro, bromo or iodo, optionally with heat and 
catalyst. 
The pharmaceutical compositions of the present invention include both 
solids or powders and solutions comprising one or more of the compounds of 
formula I in combination with a suitable pharmaceutical solvent or 
dispersant, i.e., sterile water or pharmaceutical solid excipients. 
The compounds, compositions and methods of the present invention herein 
before disclosed will become more readily apparent from the following 
description. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The compounds of the present invention of formula I are subgenerically 
represented by the formulas described below. 
##STR6## 
where R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to 
C.sub.6 alkyl; C.sub.5 to C.sub.6 cycloalkyl; C.sub.5 to C.sub.6 
cycloalkenyl; phenyl optionally substituted with a substituent selected 
from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and 
halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected 
from the group oxygen, nitrogen and sulfur; X is selected from the group 
methanesulfonate, benzenesulfonate, p-toluenesulfonate, chloride, bromide 
and iodide; and n is the integer 4 or 5. 
In the compounds of the present invention of formula II R.sup.1 and R.sup.2 
are the same or different and are preferably C.sub.1 to C.sub.4 alkyl, 
cyclopentyl, cyclohexyl, cyclopent-2-enyl, cyclohex-3-enyl, phenyl 
optionally substituted with a substituent selected from the group C.sub.1 
to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, chloro and bromo, or thienyl 
and X is selected from the group methanesulfonate, benzenesulfonate, 
chloride and bromide. 
Most preferred compounds of formula II are those where R.sup.1 and R.sup.2 
are the same or different and are methyl, ethyl, cyclopentyl, cyclohexyl, 
phenyl or thienyl and X is chloride or bromide. 
Particularly preferred compounds of formula II are: 
2-(2,2-diphenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2,2-diphenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane chloride; 
2-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-5-azoniaspiro[4.4]nonane 
chloride; and 
2-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-5-azoniaspiro[4.4]nonane 
bromide. 
##STR7## 
wherein R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to 
C.sub.6 alkyl; C.sub.5 to C.sub.6 cycloalkyl; C.sub.5 to C.sub.6 
cycloalkenyl; phenyl optionally substituted with a substituent selected 
from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and 
halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected 
from the group oxygen, nitrogen and sulfur; X is selected from the group 
methanesulfonate, benzenesulfonate, p-toluenesulfonate, nitrate, chloride, 
bromide and iodide. 
In the compounds of the present invention of formula III R.sup.1 and 
R.sup.2 are the same or different and are preferably C.sub.1 to C.sub.4 
alkyl, cyclopentyl, cyclohexyl, cyclopent-2-enyl, cyclohex-3-enyl, phenyl 
optionally substituted with a substituent selected from the group C.sub.1 
to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, chloro and bromo, or thienyl 
and X is selected from the group nitrate, methanesulfonate, chloride and 
bromide. 
Most preferred compounds of formula III are those where R.sup.1 and R.sup.2 
are the same or different and are methyl, cyclopentyl, cyclohexyl, phenyl 
or thienyl and X is chloride or bromide. 
Particularly preferred compounds of formula III are: 
2-(2,2-diphenyl-2-hydroxyacetoxy)-8-oxa-5-azoniaspiro[4.5]decane chloride; 
2-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-8-oxa-5-azoniaspiro[4.5]decane 
chloride; and 
2-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-8-oxa-5-azoniaspiro[4.5]decane 
bromide. 
##STR8## 
wherein R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to 
C.sub.6 alkyl; C.sub.5 to C.sub.6 cycloalkyl, C.sub.5 to C.sub.6 
cycloalkenyl; phenyl optionally substituted with a substituent selected 
from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and 
halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected 
from the group oxygen, nitrogen and sulfur; X is selected from the group 
methanesulfonate, benzenesulfonate, p-toluenesulfonate, chloride, bromide 
and iodide. 
In the compounds of the present invention of formula III R.sup.1 and 
R.sup.2 are the same or different and are preferably C.sub.1 to C.sub.4 
alkyl, cyclopentyl, cyclohexyl, cyclopent-2-enyl, cyclohex-3-enyl, phenyl 
optionally substituted with a substituent selected from the group C.sub.2 
to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, chloro and bromo, or thienyl 
and X is selected from the group methanesulfonate, benzenesulfonate, 
chloride and bromide. 
Most preferred compounds of formula IV are those where R.sup.1 and R.sup.2 
are the same or different and are i-propyl, cyclopentyl, cyclohexyl, 
phenyl or thienyl and X is bromide, iodide or methanesulfonate. 
Particularly preferred compounds of formula IV are: 
2-(2,2-diphenyl-2-hydroxyacetoxy)-8-thia-5-azoniaspiro[4.5]decane bromide; 
2-(2-hydroxy-2-isopropyl-2-phenylacetoxy)-8-thia-5-azoniaspiro[4.5]decane 
iodide; and 
2-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-8-thia-5 
-azoniaspiro[4.5]decane methanesulfonate. 
##STR9## 
wherein R.sup.1 and R.sup.2 are the same or different and are C.sub.1 to 
C.sub.6 alkyl; C.sub.5 to C.sub.6 cycloalkyl; C.sub.5 to C.sub.6 
cycloalkenyl; phenyl optionally substituted with a substituent selected 
from the group C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and 
halo; or C.sub.4 or C.sub.5 heterocyclic aryl, the heteroatom selected 
from the group oxygen, nitrogen and sulfur; X is selected from the group 
methanesulfonate, benzenesulfonate, p-toluenesulfonate, chloride, bromide 
and iodide; and R is hydrogen or C.sub.1 to C.sub.6 alkyl. 
In the compounds of the present invention of formula V R.sup.1 and R.sup.2 
are the same or different and are preferably C.sub.1 to C.sub.4 alkyl, 
cyclopentyl, cyclohexyl, cyclopent-2-enyl, cyclohex-3-enyl, phenyl 
optionally substituted with a substituent selected from the group C.sub.1 
to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, chloro and bromo, or thienyl 
and X is selected from the group methanesulfonate, benzenesulfonate, 
chloride and bromide. 
Most preferred compounds of formula V are those where R.sup.1 and R.sup.2 
are the same or different and are i-propyl, cyclopentyl, cyclohexyl, 
phenyl or thienyl and X is bromide, iodide or methanesulfonate. 
Particularly preferred compounds of formula V are the following: 
2-(2,2-diphenyl-2-hydroxyacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5]decane 
bromide; 
2-(2-hydroxy-2-isopropyl-2-phenylacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5] 
decane iodide; and 
2-(2-cyclohexyl-2-hydroxy-2-phenylacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5 
]decane methanesulfonate. 
The compounds of the present invention of formula I are made by the 
following process depicted schematically: 
##STR10## 
The initial reaction, as shown in reaction step 1 involves the 
transesterification of 1-benzyl-3-pyrrolidinol with an alkyl ester of 
R.sup.1, R.sup.2 -glycolic acid. As depicted in this step, ALK can be any 
lower alkyl group including methyl, ethyl, i-propyl, and the like. While 
the benzyl pyrrolidinol compound is the preferred starting material in 
this step, any of the prior art groups generally known as protecting 
groups can be employed as the substituent at the nitrogen atom. These 
include, for example, the groups diphenylmethyl, o-nitrobenzyl, 
p-nitrobenzyl, 3,5-dinitrobenzyl, p-methoxybenzyl, pivaloyloxymethyl, 
trichloroethyloxycarbonyl and the like. The transesterification is 
conducted in the presence of strong base, for example an alkali metal 
hydride, optionally in the presence of inert organic solvent, at times and 
temperatures sufficient to complete the reaction, typically 30 minutes to 
24 hours at 50.degree. to 150.degree., preferably 4 hours under reflux 
conditions, e.g., 100.degree.. Solvents for this reaction include the 
aliphatic hydrocarbon solvents, such as hexane, heptane, octane, etc.; and 
the aromatic solvents such as benzene toluene, etc. 
The glycolic acid ester, preferably isolated from step 1 is subjected to 
hydrogenolysis to remove the protecting group on the nitrogen atom. 
Preferably the reaction is conducted in aqueous acid solutions, most 
preferably at a pH of about 4 in the presence of a hydrogenolysis catalyst 
for a time sufficient to assure completeness of the reaction. Various 
metal catalysts known in the art can be employed in this step such 
including platinum, Raney nickel, etc. Typically the catalyst is palladium 
optionally on a substrate, e.g., carbon, aluminum oxide, barium sulfate, 
etc. The catalyst is most preferably palladium oxide or palladium black. 
The reaction is conducted at about room temperature and terminated when 
complete, i.e., after hydrogen uptake has ceased. 
Formation of the spiro compounds of formula II can be accomplished by 
treatment of the reaction intermediate of step 2 with an alkylene dihalide 
such as 1,4-dibromobutane, 1,4-dichlorobutane, 1,5-dichloropentane and the 
like or with an alkylene ditosylate or dimesylate in a suitable inert 
organic solvent in the presence of a base. Preferably the alkylene 
dihalides are employed in reaction step 3, most preferably the alkylene 
dibromides with the base being preferably an organic base such as a 
trialkylamine, e.g., tertiary amine, or a heteroaliphatic amine, e.g., 
N-methylmorpholine, quinuclidine, etc. The reaction solvent is typically 
an inert polar organic solvent such as acetonitrile, dimethylsulfoxide, 
dimethylformamide, and the like, the reaction being conducted for a time 
and at a temperature sufficient to assure completeness of reaction, 
typically 75.degree.-150.degree., for 24 to 72 hours. 
Formation of the spiro compounds of formulas III, IV and V may be effected 
under identical conditions and with identical solvents as set forth above. 
However, rather than using the 1,4- or 1,5-disubstituted alkanes, 
disubstituted alkylethers, disubstituted alkyl thioethers or disubstituted 
alkyl tertiary amines are employed. For example, in the preparation of the 
compounds of formula III, the product of reaction step 2 is treated with a 
di(haloethyl)ether, preferably 2,2'-dichloroethyl ether; in the 
preparation of the compounds of formula IV, the product of reaction step 2 
is treated with a di(haloethyl)thioether, preferably 2,2'-dichloroethyl 
thioether; and in the preparation of the compounds of formula V, the 
product of reaction step 2 is treated with a di(haloethyl)tertiary amine, 
preferably 2,2'-dichloroethylmethylamine. 
The compounds of the invention are predominantly antagonists of acetyl 
choline and are particularly effective as bronchodilators. As such, the 
compounds of this invention are typically administered in dosages of about 
from 0.01 to 5 mg per kg. of body weight. The precise effective dosage 
will, of course, vary depending upon the mode of administration, the 
condition being treated, and the host. Where the compounds are used as 
pulmonary anticholinergics in mammals they are typically administered 
either orally, intravenously, or by inhalation. 
The compounds of the present invention can be administered in a wide 
variety of dosage forms, either alone or in combination with other 
pharmaceutically compatible medicaments, in the form of pharmaceutical 
compositions suited for oral, parenteral or aerosol administration. The 
compounds are typically administered as pharmaceutical compositions 
consisting essentially of the compounds of the invention and a 
pharmaceutical carrier. The pharmaceutical carriers can be either a solid 
material or a liquid in which the compound is dissolved, dispersed or 
suspended, and can optionally contain small amounts of preservatives 
and/or pH-buffering agents. Suitable preservatives which can be used 
include, for example, benzyl alcohol and the like. Suitable buffering 
agents include, for example, pharmaceutical phosphate salts and the like. 
The liquid compositions can, for example, be in the form of solutions, 
emulsions, suspensions, syrups, or elixirs and optionally can contain 
small quantities of preservatives and/or buffering agents, and preferably 
contain the therapeutic agents in convenient unit dosage. 
The solid compositions can take the form of tablets, powders, capsules, 
pills and the like, preferably in unit dosage forms for simple 
administration or precise dosages. Suitable solid carriers include, for 
example, pharmaceutical grades of starch, lactose, sodium saccharine, 
sodium bisulfite and the like. 
Also based on studies on related compounds, it can be predicted that a 
number of the present compounds will exhibit useful anticholinergic 
activity when administered topically, intradermally, or subcutaneously. 
The compounds of formula I can be administered as racemic mixtures or they 
can be administered as resolved enantiomers or optical isomers. In some 
instances, one enantiomer or optical isomer exhibits a greater 
anticholinergic effect than does the other corresponding enantiomer or 
optical isomer. 
As used in the specification and the appended claims, the following terms 
have the meaning indicated. The term "C.sub.1 to C.sub.6 alkyl" refers to 
a straight or branched chain, monovalent substituent consisting solely of 
carbon and hydrogen, containing no unsaturation, and having from 1 to 6 
carbon atoms. Examples of such alkyl groups are methyl, ethyl, n-propyl, 
i-propyl, n-butyl, t-butyl, n-hexyl, 2-methylpentyl and the like. The term 
"C.sub.1 to C.sub.6 alkoxy" refers to the above disclosed alkyl groups 
linked through an ether linkage, having the free valence from the ether 
oxygen. Examples of such groups include methoxy, ethoxy, n-propoxy, 
i-propoxy, n-butoxy, t-butoxy, n-hexyloxy, and the like. The term "C.sub.5 
to C.sub.6 cycloalkyl" refers to a 5 or 6 membered monovalent ring 
containing only hydrogen and carbon that is fully saturated such as 
exemplified by cyclopentyl or cyclohexyl. "C.sub.5 to C.sub.6 
cycloalkenyl" differs from the above cycloalkyl by having in the ring at 
least one unsaturated site. Such includes 1-, 2- or 3-cyclopentenyl, 1-, 
2-, or 3-cyclohexenyl, 1,4-cyclohexadienyl, 1,3-cyclopentadienyl, and the 
like. The term "halide" refers to fluoride, chloride, bromide and iodide. 
The term "heterocyclic aryl, the heteroatom selected from oxygen, nitrogen 
and sulfur" is intended to mean the monovalent heterocyclic radicals of 
aromatic character containing, in addition to the heteroatom, 4 or 5 
carbon atoms in the ring. Examples of these radicals are pyrryl, for 
example 2- or 3-pyrryl, pyridyl, for example 2-, 3- or 4-pyridyl, thienyl, 
for example 2- or 3-thienyl and furyl, for example 2-furyl or 3-furyl. 
"Phenyl optionally substituted with a substituent selected from the group 
C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkoxy and halo" is intended 
to include unsubstituted phenyl, monosubstituted phenyl and 
polysubstituted phenyl. Such include methylphenyl, for example 2- or 
3-methylphenyl, dimethylphenyl, for example 2,4- or 3,5-dimethylphenyl, 
methoxyphenyl, for example 2- or 3-methoxyphenyl, dimethoxyphenyl for 
example 2,4- or 3,5-dimethoxyphenyl, halophenyl for example 
4-chlorophenyl, or 4-bromophenyl, or dihalophenyl, for example 
2,4-dichlorophenyl or 2,4-dibromophenyl. 
The compounds of formula I may possess a chiral center. Accordingly, the 
compounds of the invention may be prepared in either their optically 
active form or as a racemic mixture. Unless otherwise specified, the 
compounds described herein are all in the racemic form. However, the scope 
of the subject invention is not to be considered limited to the racemic, 
form, but to encompass the individual optical isomers of the compounds of 
the present invention. 
Where desired the individual diastereomeric and optically isomeric 
compounds can be isolated by conventional separation and purification 
procedures in the case of diastereomers and by conventional resolution 
procedures in the case of optical isomers. Optimum physical, or 
physical-chemical, separation procedures and resolution procedures can be 
obtained by routine trial and error procedures well within the scope of 
those skilled in the art.

A further understanding of the invention can be had from the following 
non-limiting Preparations and Examples. As used hereinabove and below 
unless expressly stated to the contrary, all temperatures and temperature 
ranges refer to the centrigrade system and the terms ambient or room 
temperature refer to about 20.degree. C. The term percent or (%) refers to 
weight percent and the term mole and moles refers to gram moles. The term 
equivalent refers to a quantity of reagent equal in moles to the moles of 
the preceding or succeeding reactant recited in that Preparation or 
Example in the terms of moles of finite weight or volume. As noted 
earlier, compounds having asymetric centers and optical activity are 
isolated in their racemic form (.+-.) unless otherwise indicated. 
PREATION 1 
To a solution of 12 g methyl benzilate and 8.2 g 1-benzyl-3-pyrrolidinol in 
200 ml n-heptane is added 100 mg sodium hydride and the mixture refluxed 
for 4 hours, separating the methanol formed in a Dean-Stark separator. The 
cooled organic phase is washed with water and then extracted with 2N HCl. 
The aqueous phase is made alkaline with solid K.sub.2 CO.sub.3 and 
extracted with ether to give 
1-benzyl-3-(2,2-diphenyl-2-hydroxyacetoxy)pyrrolidine as an oil (18.2 g). 
In a similar manner, using the following compounds in place of methyl 
benzilate: 
methyl dimethylglycolate; 
methyl diethylglycolate; 
methyl di-n -butylglycolate; 
methyl methyl-n-butylglycolate; 
ethyl methylcyclopentylglycolate; 
ethyl dicyclopentylglycolate; 
ethyl methylcyclopent-2-enylglycolate; 
ethyl methylpentylglycolate; 
methyl methyl(3-methylphenyl)glycolate; 
methyl methyl(4-chlorophenyl)glycolate; 
methyl methylpyrrol-3-ylglycolate; 
methyl methylfur-2-ylglycolate; and 
methyl methylthien-2-ylglycolate, 
are prepared the following compounds: 
1-benzyl-3-(2,2-dimethyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-(2,2-diethyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-(2,2-di-n-butyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-(2-methyl-2-n-butyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-(2,2-dicyclopentyl)-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-[2-methyl-2-(cyclopent-2-enyl)-2-hydroxyacetoxy]pyrrolidine; 
1-benzyl-3-(2-methyl-2-phenyl-2-hydroxyacetoxy)pyrrolidine; 
1-benzyl-3-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]pyrrolidine; 
1-benzyl-3-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]pyrrolidine; 
1-benzyl-3-[2-methyl-2-(pyrrol-3-yl)-2-hydroxyacetoxy]pyrrolidine; 
1-benzyl-3-[2-methyl-2-(fur-2-yl)-2-hydroxyacetoxy]pyrrolidine; and 
1-benzyl-3-[2-methyl-2-(thien-2-yl)-2-hydroxyacetoxy]pyrrolidine; 
1-benzyl-3-(2,2-diphenyl-2-hydroxyacetoxy)pyrrolidine. 
PREATION 2 
18.2 g of the amino ester of Preparation 1 is dissolved in 900 ml ethanol, 
and sufficient ethanolic hydrochloric acid is added to obtain a pH of 
about 4. The resulting solution is hydrogenated over 2.2 g 10% palladium 
on carbon at normal pressure and room temperature. After hydrogen uptake 
has ceased (about 1.2 l), the solution is filtered through Celite and the 
filtrate concentrated to about 100 ml on a rotary evaporator. The residue 
is diluted with 500 ml water, made alkaline with solid potassium 
carbonate, and extracted with ether to give 12.4 g of 
3-(2,2-diphenyl-2-hydroxyacetoxy)pyrrolidine, an oil which can be 
crystallized from ether/hexane. mp. 123.degree.-124.degree.. 
In a similar manner, the benzylpyrrolidines of Preparation I are converted 
into their respective pyrrolidines. 
EXAMPLE 1 
A solution of 12.4 g of the secondary amine of Preparation 2, 11 g of 
1,4-dichlorobutane and 8 ml of triethylamine in 180 ml acetonitrile is 
refluxed for 48 hours. The cooled reaction mixture is evaporated to 
dryness, the residue dissolved in 350 ml water and extracted with ether. 
The aqueous phase is extracted continuously with ethyl acetate for 48 
hours to give 8.3 g of 
2-(2,2-diphenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride, mp 
150.degree.-152.degree. (from MeOH/AcOEt). 
In a similar manner the pyrrolidines illustrated in Preparation 2 are 
converted into the following compounds: 
2-(2,2-dimethyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2,2-dimethyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-(2,2-diethyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2,2-diethyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-(2,2-di-n-butyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2,2-di-n-butyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-(2-methyl-2-n-butyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2-methyl-2-n-butyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane 
chloride; 
2-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane 
bromide; 
2-(2,2-dicyclopentyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2,2-dicyclopentyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-[2-methyl-2-(cyclopent-2'-enyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonan 
e chloride; 
2-[2-methyl-2-(cyclopent-2'-enyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decan 
e bromide; 
2-(2-methyl-2-phenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.4]nonane chloride; 
2-(2-methyl-2-phenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane bromide; 
2-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonane 
chloride; 
2-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decane 
bromide; 
2-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonane 
chloride; 
2-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decane 
bromide; 
2-[2-methyl-2-(pyrrol-3-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonane 
chloride; 
2-[2-methyl-2-(pyrrol-3-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decane 
bromide; 
2-[2-methyl-2-(fur-2-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonane 
chloride; 
2-[2-methyl-2-(fur-2-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decane 
bromide; 
2-[2-methyl-2-(thien-2-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.4]nonane 
chloride; 
2-[2-methyl-2-(thien-2-yl)-2-hydroxyacetoxy]-5-azoniaspiro[4.5]decane 
bromide; and 
2-(2,2-diphenyl-2-hydroxyacetoxy)-5-azoniaspiro[4.5]decane chloride, mp 
237.degree.-238.degree.. 
EXAMPLE 2 
A solution of 2.2 g of the secondary amine of Preparation 2, 2.2 g of 
2,2'-dichloroethyl ether, and 1.0 g of triethylamine in 40 ml acetonitrile 
is refluxed for 72 hours. The crystalline material that deposits on 
cooling is filtered off, washed with a little acetone, and recrystallized 
from isopropanol affording 
2-(2,2-diphenyl-2-hydroxyacetoxy)-8-oxa-5azoniaspiro[4.5]decane chloride, 
2.1 g, mp. 266.degree.-267.degree.. 
In a similar manner, the pyrrolidines illustrated in Preparation 2 are 
converted into the following compounds: 
(by reaction with 2,2'-dichloroethyl ether) 
2-(2,2-dimethyl-2-hydroxyacetoxy)-8-oxa-5-azoniaspiro[4.5]decane chloride; 
2-(2,2-dicyclopentyl-2-hydroxyacetoxy)-8-oxa-5-azoniaspiro[4.5]decane 
chloride; 
2-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)-8-oxa-5-azoniaspiro[4.5]decane 
chloride; 
2-[2-methyl-2-(cyclopent-2-enyl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5] 
decane chloride; 
2-(2-methyl-2-phenyl-2-hydroxyacetoxy)-8-oxa-5-azoniaspiro[4.5]decane 
chloride; 
2-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5]de 
cane chloride; 
2-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5]de 
cane chloride; 
2-[2-methyl-2-(pyrrol-3'-yl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5]deca 
ne chloride; 
2-[2-methyl-2-(fur-2'-yl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5]decane 
chloride; and 
2-[2-methyl-2-(thien-2'-yl)-2-hydroxyacetoxy]-8-oxa-5-azoniaspiro[4.5]decan 
e chloride. 
(by reaction with 2,2'-dichloroethyl thioether) 
2-(2,2-dimethyl-2-hydroxyacetoxy)-8-thia-5-azoniaspiro[4.5]-decane 
chloride; 
2-(2,2-dicyclopentyl-2-hydroxyacetoxy)-8-thia-5-azoniaspiro[4.5]-decane 
chloride; 
2-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)-8-thia-5-azoniaspiro[4.5]decane 
chloride; 
2-[2-methyl-2-(cyclopent-2'-enyl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4. 
5]decane chloride; 
2-(2-methyl-2-phenyl-2-hydroxyacetoxy)-8-thia-5-azoniaspiro[4.5]decane 
chloride; 
2-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4.5]d 
ecane chloride; 
2-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4.5]d 
ecane chloride; 
2-[2-methyl-2-(pyrrol-3-yl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4.5]deca 
ne chloride; 
2-2-methyl-2-(fur-2-yl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4.5]decane 
chloride; and 
2-[2-methyl-2-(thien-2-yl)-2-hydroxyacetoxy]-8-thia-5-azoniaspiro[4.5]decan 
e chloride. 
(by reaction with 2,2'-dichloroethylmethylamine) 
2-(2,2-dimethyl-2-hydroxyacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5]-decane 
chloride; 
2-(2,2-dicyclopentyl-2-hydroxyacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5]-de 
cane chloride; 
2-(2-methyl-2-cyclopentyl-2-hydroxyacetoxy)-8-aza-8-methyl-5-azoniaspiro[4. 
5]decane chloride; 
2-[2-methyl-2-(cyclopent-2-enyl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azonias 
piro[4.5]decane chloride; 
2-(2-methyl-2-phenyl-2-hydroxyacetoxy)-8-aza-8-methyl-5-azoniaspiro[4.5]dec 
ane chloride; 
2-[2-methyl-2-(3-methylphenyl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azoniaspi 
ro[4.5]decane chloride; 
2-[2-methyl-2-(4-chlorophenyl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azoniaspi 
ro[4.5]decane chloride; 
2-[2-methyl-2-(pyrrol-3-yl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azoniaspiro[ 
4.5]decane chloride; 
2-[2-methyl-2-(fur-2'-yl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azoniaspiro[4. 
5]decane chloride; and 
2-[2-methyl-2-(thien-2'-yl)-2-hydroxyacetoxy]-8-aza-8-methyl-5-azoniaspiro[ 
4.5]decane chloride. 
While the present invention has been described with reference to specific 
embodiments thereof, it should be understood by those skilled in the art 
that various changes may be made and equivalents may be substituted 
without departing from the true spirit and scope of the invention. In 
addition, many modifications can be made to adapt a particular situation, 
material or composition of matter, process, process step or steps or 
objective to the spirit of this invention without departing from its 
essential teachings.