1-Aryloxy-4-amino-2-butanols and the pharmaceutical use thereof

Novel 1-aryloxy-4-amino-2-butanols of the formula EQU ArO--CH.sub.2 --CHOH--CH.sub.2 --CH.sub.2 --NR.sup.1 R.sup.2 wherein Ar is 1-naphthyl, 2-naphthyl, indene-4(or 5-)yl, 3-(or 5-)chloro-2-pyridyl, phenyl, monosubstituted phenyl or di-substituted phenyl, R.sup.1 is lower alkyl, phenyl, phenylalkyl, 2-hydroxymethyl-2-propyl, adamantyl or lower-cycloalkyl, R.sup.2 is hydrogen or lower alkyl, wherein R.sup.1 and R.sup.2 together with the adjacent nitrogen form a heterocyclic residue and the pharmaceutically acceptable acid addition salts thereof having local anesthetic, beta-adrenergic blocking, antihypertensive and antiarrhythmic properties are disclosed. The compounds are prepared by reacting novel 1-aryloxy-4-chloro-2-butanols with amines. Methods for the preparation of the novel 1-aryloxy-4-chloro-2-butanol intermediates are also disclosed.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to certain organic compounds which may be 
referred to as disubstituted-2-butanols and is more particularly concerned 
with 1-aryloxy-4-amino-2-butanols and with processes for the production 
thereof, intermediate products useful in the preparation thereof and with 
processes for the preparation of such intermediates, compositions 
containing the 1-aryloxy-4-amino-2-butanols as active ingredients and 
methods for the use thereof. 
2. Discussion of the Prior Art 
The compounds which are the subject of this invention are related to known 
1-aryloxy-3-amino-2-propanols as having beta-adrenergic blocking, 
anticonvulsant, sedative and tranquilizing activity. Among the United 
States patents disclosing the aforementioned 1,3-disubstituted-2-propanols 
and their pharmacological properties are U.S. Pat. Nos. 3,337,628; 
3,415,873; 3,432,545 and 3,520,919. U.S. Pat. No. 3,337,628 in particular 
discloses 1-isopropyl-amino-3-(1-naphthyloxy)-2-propanol which compound is 
a potent beta-adrenergic blocking agent. 
SUMMARY OF THE INVENTION 
The present invention is especially concerned with novel 
1-aryloxy-4-amino-2-butanols having the formula: 
EQU ArO--CH.sub.2 --CHOH--CH.sub.2 --CH.sub.2 --NR.sup.1 R.sup.2Formula I 
wherein; 
Ar is 1-naphthyl, 2-naphthyl, indene-4(or 5-)yl, 3-(or 5-) 
chloro-2-pyridyl, phenyl, monosubstituted phenyl or disubstituted phenyl, 
R.sup.1 is lower alkyl, phenyl, phenylalkyl, 2-hydroxymethyl-2-propyl, 
adamantyl or lower cycloalkyl, 
R.sup.2 is hydrogen or lower alkyl, 
R.sup.1 and R.sup.2 together with the adjacent nitrogen form a heterocyclic 
residue, and 
pharmaceutically acceptable acceptable acid addition salts thereof. 
The compounds of the invention having the foregoing Formula I are generally 
characterized by important and significant pharmacological activity, which 
is indicative of their use in counteracting certain physiological 
abnormalities in an animal body. The compounds possess local anesthetic, 
beta-adrenergic blocking, anti-hypertensive and antiarrhythmic properties. 
The 1-aryloxy-4-amino-2-butanols were evaluated for pharmacological 
activity and were found to possess antiarrhythmic properties against 
experimentally induced cardiac arrhythmias in dogs. The prior art homolog 
1,3-disubstituted-2-propanols also have antiarrhythmic activity. However, 
in contrast to the prior art 2-propanols, the novel 2-butanols of the 
present invention have minimal beta-adrenergic blocking activity, enabling 
them to be employed in controlling moderate to serious arrhythmias without 
the dangers of cadiac failure and respiratory difficulties, which dangers 
are attendant when the prior art 1,3-disubstituted-2-propanols having 
potent beta-adrenergic blocking activity are used in controlling cardiac 
arrhythmias. 
Compounds of Formula I wherein Ar is 1-naphthyl and --NR.sup.1 R.sup.2 is 
lower-alkylamino, lower cycloalkylamino wherein lower cycloalkyl has from 
5 to 7 carbon atoms, phenylalkylamino, 2-hydroxymethyl-2-propylamino or 
phenylamino represent preferred compounds for their antiarrhythmic 
activity. 
Compounds of Formula I wherein Ar is an ortho-lower-alkoxyphenoxy radical, 
particularly methoxy- and ethoxy- phenoxy radicals, and --NR.sup.1 R.sup.2 
is lower-alkylamino, lower cycloalkylamino wherein lower cycloalkyl has 
from 5 to 7 carbon atoms, phenylalkylamino, 2-hydroxymethyl-2-propylamino 
or phenylamino are also of particular interest for their antiarrhythmic 
activity. 
To illustrate the utility of the compounds of this invention the following 
tabulation indicates the amount of certain representative compounds of 
this invention to correct ouabain-induced arrhythmias in anesthetized 
dogs. 
TABLE 1 
______________________________________ 
Average Corrective 
No. of 
Example Dose (mg/kg, i.v.) 
Tests 
______________________________________ 
46 12.5 1 
47 7.0 2 
1 2.75 2 
14 19.0 2 
15 3.5 2 
17 5.0 2 
7 1.75 2 
19 9.3 2 
6 5.5 1 
23 9.3 2 
3 3.5 2 
28 3.0 2 
30 2.0 2 
37 8.0 1 
42 2.25 2 
73 3.25 2 
74 2.5 1 
75 4.0 2 
______________________________________ 
It is accordingly an object of this invention to provide novel 
1-aryloxy-4-amino-2-butanols which are useful pharmacologically because of 
their aforesaid types of activity, processes for the production thereof, 
and intermediate products useful in the preparation thereof and processes 
for the production of such intermediates which in themselves have useful 
pharmacological activity. A further object is to provide novel 
compositions containing 1-aryloxy-4-amino-2-butanols as active ingredients 
and methods for their use. Other objects of the invention will be apparent 
to one skilled in the art, and still other objects will become apparent 
hereinafter. 
In the definitions of the symbols in foregoing Formula I and where they 
appear elsewhere throughout this specification, the terms have the 
following significance. 
The term "lower alkyl" as used herein includes straight and branched chain 
radicals of up to eight carbon atoms inclusive and is exemplified by such 
groups as methyl, ethyl, propyl, isopropyl, tertiary butyl, amyl, isoamyl, 
hexyl, heptyl, octyl, and the like. 
The term "lower alkoxy" has the formula -O-lower alkyl. 
When halogen is referred to herein, preferably but not necessarily, a 
halogen of atomic weight in excess of eighteen but not greater than eighty 
is employed. 
The term "heterocyclic residue" as used herein includes basic saturated 
monocyclic heterocyclic radicals and basic unsaturated monocyclic 
heterocyclic radicals of less than twelve carbon atoms, as exemplified by 
piperidino; (lower alkyl) piperidino, e.g., 2-, 3-, or 4-(lower 
alkyl)piperidino; pyrrolidino; morpholino; di-(lower alkyl)morpholino, 
e.g., 3,5-dimethylmorpholino; 2,6-dimethylmorpholino; piperazino; (lower 
alkyl)piperazino (e.g., N.sup.4 -methylpiperazino); phenylpiperazino 
(e.g., N.sup.4 -phenylpiperazino); 1,2,3,4-tetrahydroisoquinolyl; 
1,2,5,6-tetrahydropyridino, 4-(2-pyridyl)piperazino, and phthalimido. 
Included in the term "phenylalkyl" are groups such as benzyl, phenethyl, 
methylbenzyl, phenpropyl, and the like. 
The term "lower cycloalkyl" includes cyclic radicals having up to eight 
carbon atoms and includes radicals such as cyclopropyl, cyclobutyl, 
cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. 
The term "phenyl" includes the unsubstituted phenyl radical, the 
substituted phenyl radical and the disubstituted phenyl radical. Among the 
suitable substituted and disubstituted phenyl radicals are those which are 
substituted by any radical or radicals which are not reactive or otherwise 
interfering under the conditions of reaction in preparing the desired 
compound, such radicals including lower alkyl, lower alkoxy, 
trifluoromethyl, acetyl, acetylamino, halo, trifluoromethyl, and phenyl. 
The substituted phenyl radicals have preferably one or two substituents 
such as those given above and, furthermore, the substituents can be in 
various available positions of the phenyl nucleus and, when more than one 
substituent is present, can be the same or different and can be in various 
combinations relative to each other. The lower alkyl and lower alkoxy 
substituents each have preferably from one to four carbon atoms which can 
be arranged as straight or branched chains. A total of nine carbon atoms 
in all ring substituents, making a total of fifteen carbon atoms in the 
radical, is the preferred maximum. 
The compounds of the invention are most conveniently employed in the form 
of pharmaceutically acceptable acid addition salts. Such salts have 
improved water solubility over the free bases. Appropriate acid addition 
salts are those derived from mineral acids such as hydrochloric, 
hydrobromic, sulfuric and phosphoric; and organic acids such as acetic, 
citric, lactic, maleic, oxalic, fumaric and tartaric. The preferred acid 
addition salt is the hydrochloride. The acid addition salts are 
conveniently prepared by reaction of the basic compounds with the selected 
acid, either or both of which may be in the form of ether, alcohol or 
acetone solutions. 
The present invention also includes the novel 1-aryloxy-4-chloro-2-butanols 
of Formula IV which are useful as intermediates for preparing the final 
amine products of Formula I and they may be prepared by the process 
diagrammed in Chart I, wherein all of the symbols have the meanings given 
previously. 
CHART I-PREATION OF STARTING 1-ARYLOXY-4-CHLORO-2-BUTANOLS (IV) 
##STR1## 
The 1-aryloxy-4-chloro-2-butanols (IV) are generally prepared by treating 
an aqueous basic solution or an aqueous-alcoholic basic solution of a 
phenol, a substituted phenol or an aryl compound having an acidic hydroxyl 
group of Formula II with 1,4-dichloro-2-butanol III. The addition is 
carried out at or below 70.degree. C., preferably at from about 30.degree. 
C. to about 65.degree. C. over a period of from about three hours to about 
eight hours. Subsequent to the addition the reaction mixture is heated at 
from about 50.degree. C. to about 75.degree. C., preferably at 60.degree. 
C. to 70.degree. C. for a period of from about six hours to about 
forty-eight hours, usually for a period of from twelve hours to eighteen 
hours. The 1-aryloxy-4-chloro-2-butanol is isolated from the reaction 
mixture by extraction using a suitable organic solvent as, for example, 
ether, isopropyl ether or chloroform, evaporation of the solvent after 
drying to give the 2-butanol which is isolated by suitable means such as 
distillation or crystallization. Alternatively, the 
1-aryloxy-4-chloro-2-butanol can be prepared by adding an aqueous basic 
solution to a mixture of the phenol or the compound having an acidic 
hydroxyl group and 1,4-dichloro-2-butanol at a rate so as to maintain the 
reaction mixture at a pH of from about 9.0 to about 10.5, preferably at a 
pH of 9.5 to 10.0. The product is isolated as described hereinabove. 
The following preparations are given by way of illustration only and are in 
no event to be construed as limiting. 
PREATION 1 
4-Chloro-1-phenoxy-2-butanol 
To a mixture which contained 282 g. (3 moles) of phenol, one liter of water 
and 300 ml. of 50% sodium hydroxide was added slowly with stirring at 
60.degree. C. 443.36 g. (3.1 moles) of 1,4-dichlorobutanol. Stirring was 
continued at 60.degree. C. for 16 hr. The resulting mixture was extracted 
twice with one liter of ether and the combined ether extracts were washed 
with water to neutrality and dried overnight over sodium sulfate. The 
dried ether mixture was concentrated to dryness under reduced pressure. 
The residue was distilled and yielded 435 g. of product which was 
collected at 135.degree.-138.degree. C./0.05 mm. The product solidified 
and was recrystallized using pet. ether (60.degree.-110.degree. C.) to 
give a white crystalline solid which melted at 52.degree.-54.degree. C. 
Analysis: Calculated for C.sub.10 H.sub.13 ClO.sub.2 : C, 59.86; H, 6.53, 
Found: C, 59.72; H, 6.37. 
PREATION 2 
4-Chloro-1-(2-chlorophenoxy)-2-butanol 
To a mixture of 129 g. (1 mole) of 2-chlorophenol, 60 g. of potassium 
hydroxide, 100 ml. of water and 400 ml. of isopropanol was added 1.3 moles 
(185.9 g.) of 1,4-dichloro-2-butanol with stirring at 50.degree. C. The 
resulting mixture was heated in a steam bath at 65.degree. C. overnight 
and extracted with 300 ml. of isopropyl ether. The ether extract was 
washed successively with 1 N sodium hydroxide, water and dried over sodium 
sulfate. The dried ether solution was concentrated and the oily residue 
was distilled under reduced pressure yielding 152 g. of an oily substance 
(b.p. 130.degree.-131.degree. C./0.01 mm.). 
Analysis: Calculated for C.sub.10 H.sub.15 ClO.sub.2 : C, 51.08; H, 5.15, 
Found: C, 51.13; H, 5.14. 
PREATION 3 
4-Chloro-1-(3,5-dimethylphenoxy)-2-butanol 
To a mixture of 245 g. (2 moles) of 3,5-dimethylphenol and 2 liters of 2 N 
sodium hydroxide was added 2.5 moles of 1,4-dichlorobutanol with stirring 
at 65.degree. C. overnight. The solid precipitate which separated on 
cooling was filtered and washed with water to neutrality. 
Recrystallization with isopropyl ether yielded 375 g. of white crystalline 
solid which melted at 74.degree.-76.degree. C. 
Analysis: Calculated for C.sub.12 H.sub.17 ClO.sub.2 : C, 62.02; H, 7.49, 
Found: C, 63.96; H, 7.66. 
PREATION 4 
4-Chloro-1-(4-chloro-3-methylphenoxy)-2-butanol 
To a mixture of 286 g. (2 moles) of 3-methyl-4-chlorophenol, 700 ml. of 
tertiary butanol, 700 ml. of water and 3.0 moles of 
1,4-dichloro-2-butanol, sodium hydroxide (2.9 moles, 230 g. in 700 ml. 
water) was added with stirring at 40.degree. C. to maintain a pH of 
9.5-10.0 as the reaction progressed. The addition was 10 hr.; the reaction 
was stirred at 40.degree. C. for 48 hr. The resulting reaction mixture was 
extracted with chloroform sodium hydroxide at 25.degree. C. The chloroform 
extract was washed with sodium sulfate. The dried chloroform solution was 
concentrated and the residue was distilled under reduced pressure to give 
110.9 g. of the product which distilled at 135.degree.-143.degree. 
C./0.007 mm. and melted at 87.degree.-89.degree. C. after 
recrystallization with isopropanol and pet. ether (30.60.degree.). 
Analysis: Calculated for C.sub.11 H.sub.14 Cl.sub.2 O.sub.2 : C, 53.03; H, 
5.66, Found: C, 53.11; H, 5.61. 
PREATION 5 
4-Chloro-1-(4-chloro-2-methylphenoxy)-2-butanol 
4-Chloro-1-(4-chloro-2-methylphenoxy)-2-butanol was prepared according to 
the procedure of Preparation 4 using 105 g. (0.74 mole) of 
2-methyl-4-chlorophenol, 171.5 g. (1.2 mole) of 1,4-dichloro-2-butanol, 
50.3 g. of sodium hydroxide, 300 ml. of water and 300 ml. of tertiary 
butanol. There was obtained 84 g. (45.5%) of product which distilled at 
135.degree. C./0.01 mm. 
Analysis: Calculated for C.sub.11 H.sub.14 O.sub.2 Cl.sub.2 : C, 53.03; H, 
5.66; Found: C, 53.41; H, 5.70. 
PREATION 6 
4-Chloro-1-(1-naphthyloxy)-2-butanol 
To a mixture of 1 mole (147 g.) of 1-naphthol, 350 ml. of water and 2 moles 
(112 g.) of potassium hydroxide was added at 54.degree. C. 1 mole (143 g.) 
of 1,4-dichloro-2-butanol. The temperature of the reaction mixture was 
kept below 60.degree. C. during the addition of the chlorobutanol. The 
reaction mixture was heated at 65.degree. C. for 12 hr., then mixed with 
500 ml. of water and 350 ml. of chloroform. The chloroform layer was 
separated, washed with water, dried over sodium sulfate, concentrated and 
the residual oil distilled under reduced pressure to give 128 g. of a 
crystalline solid which was distilled at 162.degree.-165.degree. C./0.01 
mm. The solid was recrystallized with ether and pet. ether 
(30.degree.-60.degree.) to give material melting at 75.degree.-77.degree. 
C. 
Analysis: Calculated for C.sub.14 H.sub.15 O.sub.2 Cl: C, 67.07; H, 6.03, 
Found: C, 67.19; H, 6.19. 
PREATION 7 
4-Chloro-(4-biphenylyloxy)-2-butanol 
To a solution of 1 mole (158 g.) of 4-phenylphenol 100 g. of sodium 
hydroxide and 500 ml. of water was added 1 mole (143.02 g.) of 
1,4-dichloro-2-butanol with stirring at 40.degree. C. The resulting 
mixture was heated at 68.degree. C. in a steam bath for 6 hr., cooled and 
extracted with 300 ml. of chloroform. The chloroform extract was washed 
with water to neutrality, dried over sodium sulfate and concentrated to 
dryness. The solid residue was recrystallized with isopropanol and yielded 
180 g. of a white crystalline solid which melted at 
123.degree.-124.degree. C. 
Analysis: Calculated for C.sub.16 H.sub.17 ClO.sub.2 : C, 69.44; H, 6.19, 
Found: C, 69.79; H, 6.22. 
PREATION 8 
4-Chloro-1-(3-trifluoromethylphenoxy)-2-butanol 
To a mixture of 0.5 mole (75 g.) of m-trifluoromethylphenol, 1 mole (56 g.) 
of potassium hydroxide, 100 ml. of water and 400 ml. of isopropanol was 
added 0.6 mole (84 g.) of 1,4-dichloro-2-butanol with stirring at 
temperature below 55.degree. C. The resulting reaction mixture was heated 
at 65.degree. C. for 20 hr., mixed with 2 liters of water, and extracted 
with 400 ml. of isopropyl ether. The ether extract was washed with 0.5 N 
sodium hydroxide and then with water, dried over sodium sulfate and 
distilled under reduced pressure. The distillate which was collected at 
120.degree.-124.degree. C./0.01 mm. solidified at room temperature and 
melted at 50.degree.-52.degree. C. 
Analysis: Calculated for C.sub.11 H.sub.12 ClF.sub.3 O.sub.2 : C, 49.18; H, 
4.50, Found: C, 49.35; H, 4.47. 
PREATION 9 
4-Chloro-1-(4-chlorophenoxy)-2-butanol 
4-Chloro-1-(4-chlorophenoxy)-2-butanol was prepared using the procedure of 
Preparation 7 from 45 g. (0.5 mole) of p-chlorophenol, 72 g. (0.5 mole) of 
1,4-dichloro-2-butanol, 40 g. (1.0 mole) of sodium hydroxide and 400 ml. 
of water to give 85 g. (36.1%) of product which melted at 
62.degree.-64.degree. C. after recrystallization from isopropanol. 
Analysis: Calculated for C.sub.10 H.sub.15 ClO.sub.2 : C, 51.09; H, 5.14, 
Found: C, 51.76; H, 5.12. 
PREATION 10 
4-Chloro-1-(2-methoxyphenoxy)-2-butanol 
To a mixture of 2 moles (248.26 g.) of 2-methoxyphenol, 4 moles (160 g.) of 
sodium hydroxide, 250 ml. of water and 1 liter of isopropanol was added 
with stirring 2.2 moles (314.64 g.) of 1,4-dichloro-2-butanol. The mixture 
was refluxed gently overnight. The reaction mixture was extracted with 1 
liter of isopropyl ether, dried over sodium sulfate and distilled under 
reduced pressure. The distillate which was collected at 
136.degree.-138.degree. C./0.015 mm. (396.8 g.) solidified to a white 
crystalline solid which melted at 48.degree.-50.degree. C. 
Analysis: Calculated for C.sub.11 H.sub.14 O.sub.3 Cl: C, 57.52; H, 6.14, 
Found: C, 57.49; H, 6.54. 
Using the procedures disclosed in Preparations 1-10, starting from the 
appropriate phenol II and 1,4-dichloro-2-butanol III, various other 
1-aryloxy-4-chloro-2-butanols IV are prepared. 
PREATION 11 
4-Chloro-1-(2-methyl-5-chlorophenoxy)-2-butanol, b.p. 135.degree.-8.degree. 
C./0.05 mm. was prepared from 2-methyl-5-chlorophenol and 
1,4-dichloro-2-butanol. 
PREATION 12 
4-Chloro-1-(2-naphthyloxy)-2-butanol, m.p. 101.degree.-102.degree. C., was 
prepared from 2-naphthol and 1,4-dichloro-2-butanol. 
PREATION 13 
4-Chloro-1-(4-acetylaminophenoxy)-2-butanol, m.p. 125.degree.-128.degree. 
C., was prepared from 4-acetylaminophenol and 1,4-dichloro-2-butanol. 
PREATION 14 
4-Chloro-1-(4-methoxyphenoxy)-2-butanol, m.p. 61.degree.-63.degree. C., was 
prepared from 4-methoxyphenol and 1,4-dichloro-2-butanol. 
PREATION 15 
4-Chloro-1-(3-chloro-2-pyridyloxy)-2-butanol, m.p. 56.degree.-58.degree. 
C., was prepared from 3-chloro-2-hydroxypyridine and 
1,4-dichloro-2-butanol. 
PREATION 16 
4-Chloro-1-(5-chloro-2-pyridyloxy)-2-butanol, was prepared from 
5-chloro-2-hydroxypyridine and 1,4-dichloro-2-butanol. 
PREATION 17 
4-Chloro-1-(inden-5-yloxy)-2-butanol, m.p. 56.degree.-58.degree. C., was 
prepared from 6-hydroxyindene and 1,4-dichloro-2-butanol. 
PREATION 18 
4-Chloro-1-(3-chlorophenoxy)-2-butanol, 60.degree.-62.degree. C., was 
prepared from 3-chlorophenol and 1,4-dichloro-2-butanol. 
PREATION 19 
4-Chloro-1-(2-ethoxyphenoxy)-2-butanol, b.p. 130.degree.-132.degree. 
C./0.01 mm. was prepared from 2-ethoxyphenol and 1,4-dichloro-2-butanol. 
PREATION 20 
4-Chloro-1-(4-acetylphenoxy)-2-butanol, m.p. 125.degree.-128.degree. C., 
was prepared from 4-acetylphenol and 1,4-dichloro-2-butanol. 
PREATION 21 
4-Chloro-1-(o-phenylphenoxy)-2-butanol, b.p. 156.degree.-160.degree. 
C./0.25 mm., was prepared from o-phenylphenol and 1,4-dichloro-2-butanol. 
The preparation of the novel 1-aryloxy-4-amino-2-butanols of the present 
invention is designated in the following reaction sequence: 
CHART 2-PREATION OF 1-ARYLOXY-4-AMINO-2-BUTANOLS 
##STR2## 
wherein all of the symbols have the meanings given hereinabove. 
In the reaction sequence the 1-aryloxy-4-chloro-2-butanol (IV) is reacted 
with an amine (V) to give the novel 1-aryloxy-4-amino-2-butanols (I). The 
foregoing reaction can be carried out by (A) heating a mixture of the 
chloro compound and the amine with a solvent in a steel bomb, (B) heating 
a mixture of the chloro compound and the amine without a solvent in a 
steel bomb, (C) refluxing a mixture of the chloro compound, the amine and 
a solvent at atmospheric pressure or (D) heating a mixture of the chloro 
compound and the amine without a solvent at atmospheric pressure and at a 
suitable temperature. The selected procedure is somewhat dependent on the 
nature of the amine reactant. Thus, when the amine is a low molecular 
volatile amine process A or B is preferred and the bomb contents are 
heated at from about 100.degree. C. to about 150.degree. C. for a period 
of from about 12 hours to about 24 hours. When the amine is a high 
molecular weight non-volatile amine or an amine having low volatility, 
process C or D is preferred and the reaction mixture is refluxed at the 
temperature of the solvent used or the mixture is heated at from about 
100.degree. C. to about 150.degree. C. The reaction time can be varied, 
reaction times being somewhat shorter when the chloro compound and the 
amine are reacted together in the absence of a solvent and a higher 
reaction temperature is employed. The reaction product in each case is 
isolated by conventional acid-base extraction procedures and the free 
base, if desired, is converted to a pharmaceutically acceptable acid 
addition salt which is further purified by crystallization from a suitable 
solvent or solvent system. 1-Aryloxy-4-amino-2-butanols which do not form 
well defined salts can be purified by vacuum distillation. 
Examples 1-6 illustrate the preparation of the novel 
1-aryloxy-4-amino-2-butanol compounds of the present invention by one of 
the four optional processes. Table I summarizes the physical data of 
additional compounds within the scope of Formula I and indicates the 
process used to prepare each compound. 
Table II contains the analytical data of the compounds listed in Table I.