Patent GB-781382-A (GB)
Title: Novel basic esters, their acid salts and quaternary salts
IPC: C07D207/12
Filed: 1954-11-08
Abstract: The invention comprises esters of b -dialkylamino-ethanols, g -dialkylaminopropanols, 1-alkyl - 4 - piperidinols and 1 - alkyl - 3 - pyrrolidinols with acids of the general formula <FORM:0781382/IV (a)/1> in which R1 represents a methyl or ethyl radical, R2 represents an ethyl, propyl or butyl radical and X represents hydrogen or OH, while Y represents hydrogen, or Y together with X represent a carbon-carbon linkage, but R1 and R2 both represent ethyl radicals in the case where the basically-substituted alcohol is b -dimethylamino-ethanol or b -diethylaminoethanol and X and Y both represent hydrogen, and acid salts and quaternary salts of said esters.  Such compounds are obtained by reacting the appropriate basic alcohol with acids of the above formula or their reactive functional derivatives, for example the halides, alkyl or aryl esters, anhydrides, mixed anhydrides such as those with sulphuric, carbonic or phosphoric acid, or the nitriles and ketones, followed if desired by conversion to salts or quaternary salts with, for example, alkyl, aralkyl or alkenyl halides or sulphates or alkyl or aryl sulphonates.  Alternatively reactive esters of basic alcohols or their quaternary compounds may be reacted with acids or salts of the above formula.  As a further method the appropriate bases can be reacted with substituted-alkyl esters of the above acids in which the substituent is a halide or an alkyl- or aryl-sulphonoxy radical. When the products are derived from acids of the above formula where X represents OH, this group can be protected by conversion to the benzyloxy or benzhydryloxy group or by replacing the hydrogen atom of the group by a carbobenzoxy radical or by reaction with halo-carboxylic acid ester, an alkyl- or aryl-sulphonic acid halide or an acyl or aroyl halide, such groups being subsequently removed by hydrogenolysis or hydrolysis.  In examples: (1) the chloride of 2-phenyl-3-methyl-pentanoic acid (from the acid and thionyl chloride) is reacted with 3-diethylaminopropanol to give the corresponding ester, which is converted to the hydrochloride; (2) the same ester is prepared by reacting pentanoic acid-(1) methyl ester with 2-diethylaminoethanol in the presence of sodium methylate; or (3) phenyl-sec.-butyl-ketene and diethylaminoethanol; (4) 3-methyl-2-phenyl-pentanoic acid-(1) is esterified with N-(3-chloropropyl)-morpholine; (5) the 3-pyrrolidinopropyl ester is prepared similarly; (6) 3-methyl-2-phenyl-pentanoic acid (1)-31-piperidino-propyl ester is reacted with methyl bromide to give the quaternary compound; (7) 3-methyl-2-phenyl-pentene-(2)-acid-(1) is esterified by reaction with diethylaminoethyl chloride; (8) 2-hydroxy - 2 - phenyl - 3 - methyl - pentanoic acid and diethyl aminoethyl chloride are reacted to give the corresponding ester; (9) the 3-diethylaminopropyl ester is prepared similarly.  There are also described the 2-dimethylaminoethyl, 2 - diisopropylaminoethyl, 2 - pyrrolidinoethyl, 2 - piperidinoethyl, 2 - lupetidinoethyl, 2 - morpholinoethyl, 3 - dimethylaminopropyl, 3 - diisopropylaminopropyl, 3 - piperidinopropyl, 3 - lupetidinopropyl, 2 - diethylaminopropyl, 3 - diethylaminopropyl - 2, 4 - diethylaminobutyl, 5 - diethylaminopentyl, 3-diethylamino - 2,2 - dimethylpropyl, 3 - pyrrolidino - 2,2 - dimethylpropyl, 3 - piperidino - 2,2 - dimethylpropyl 3 - morpholino - 2,2 - dimethylpropyl, 5 - diethylaminopentyl - 2, 2 - diethylaminoethoxyethyl, 1 - methylpyrrolidyl - 3, 1 - ethyl - pyrrolidylmethyl - 3, 1 - methyl-piperidyl-3 or -4, 1-ethyl-piperidyl-3 or -4, 1-dimethylamino-cyclohexyl-2 and 1-diethylamino-cyclohexyl-2 esters of 2-phenyl-2-methyl-pentanoic acid (1).  Produced analogously also are the 2-diethylaminoethyl and 3-diethylaminopropyl esters of 2-phenyl-3-ethyl-pentanoic acid and of 2-phenyl-3-methyl hexanoic acid.  Phenylacetic acids.  2 - Phenyl - 3 - methyl - pentanoic acid and homologues are obtained by reacting benzyl cyanide with 2-bromobutane or its homologues and saponifying the nitrile obtained. 2 - Phenyl - 2 - hydroxy - 3 - methyl - pentanoic acid is obtained by reacting benzoyl-formic acid alkyl ester with sec.-butyl magnesium bromide and saponifying the ester obtained.  2 - Phenyl - 3 - methyl - pentene - (2) - acid - (1) is obtained by reacting a C,O-dimagnesium salt of phenyl acetic acid with methyl ethyl ketone and heating the 2-phenyl-3-methyl-3-hydroxy-pentanoic acid-(1) obtained with glacial acetic acid/sulphuric acid to split off water. Specifications 483,704, [Group IV], and 748,064 are referred to.