Patent GB-815844-A (GB)
Title: Pyrrolidyl esters and salts thereof
Inventor: MEHTA MINOO DOSSABHOY
Filed: 1956-12-07
Abstract: The invention comprises esters of the general formula <FORM:0815844/IV (b)/1> and acid addition salts thereof, where R is a phenyl group and R1 is a phenyl or cyclohexyl group or R and R1 together with the carbon atom to which they are attached form the residue of a fluorene or xanthene ring system; R2 is hydrogen or a C1-4 alkyl group; R3 is hydrogen or a methyl group; X is hydrogen or an hydroxyl group and n is 2, 3 or 4.  Three methods of preparation are given: (a) esterifying an alcohol <FORM:0815844/IV (b)/2> with an acid halide <FORM:0815844/IV (b)/3> where X1 is H, Cl or Br and Y is Cl or Br and treating the resulting hydrohalide with a base and, where X1 is Cl or Br, with water also, e.g. by standing in aqueous solution at room temperature, usually before the treatment with base e.g. NaOH; (b) reacting an acid <FORM:0815844/IV (b)/4> or one of its salts, preferably an alkali metal salt, with a compound <FORM:0815844/IV (b)/5> (c) heating an ester <FORM:0815844/IV (b)/6> where R4 is a C1-4 alkyl group, with an alcohol of formula III, conveniently in excess and preferably in the presence of an alkali metal alkoxide, distilling off the lower alcohol produced as it is formed.  Suitable acid addition salts of the invention mentioned are the halides, sulphates, citrates and tartrates.  Examples describe the preparation by method (a) of b -(1-methyl-2-pyrrolidyl) ethyl diphenylacetate and its hydrochloride; b -(1-methyl-2-pyrrolidyl)-ethyl benzilate hydrochloride via b -(1-methyl-2-pyrrolidyl)ethyl diphenylchloracetate hydrochloride; b -(1-methyl-2-pyrrolidyl)ethyl fluorene - 9 - carboxylate hydrochloride; b  - (1-methyl - 2 - pyrrolidyl)ethyl xanthene - 9 - carboxylate hydrochloride; b  - (1 - ethyl - 2 - pyrrolidyl)ethyl diphenylacetate; b -(1-ethyl-2-pyrrolidyl)ethyl benzilate hydrochloride via b -(1-ethyl - 2 - pyrrolidyl)ethyl diphenylchloracetate hydrochloride; b  - (1,5 - dimethyl - 2 - pyrrolidyl)ethyl benzilate hydrochloride via b -(1,5-dimethyl - 2 - pyrrolidyl)ethyl diphenylchloracetate hydrochloride; b  - (1 - n - propyl - 2-pyrrolidyl)ethyl benzilate and its hydrochloride via the crude corresponding chloracetate; b -(1-benzyl-2-pyrrolidyl)ethyl benzilate which is hydrogenated using Pd/charcoal to b -(2-pyrrolidyl)ethyl benzilate; g -(1-methyl-2-pyrrolidyl) propyl benzilate and its hydrochloride via the crude chloracetate; and by method (b) b  - (1 - methyl - 2 - pyrrolidyl)ethyl phenylcyclohexylglycollate hydrochloride.  Starting materials prepared are: 1-methyl-2-(2 - hydroxyethyl) pyrrolidine, 1 - ethyl - 2 - (2-hydroxyethyl) pyrrolidine, 1,5 - dimethyl - 2 - (2-hydroxyethyl) - pyrrolidine and 1 - n - propyl-2 - (2 - hydroxyethyl) pyrrolidine by reacting the corresponding alkylpyrroles with ethyl diazoacetate to give ethyl alkylpyrrylacetates, hydrogenating these to the corresponding pyrrolidylacetates and reducing these to the hydroxyethylalkylpyrrolidines with lithium aluminium hydride; 1 - benzyl - 2 - (2 - hydroxyethyl)pyrrolidine by reacting benzyl bromide with ethyl 2 - pyrrolidylacetate prepared from pyrrole as above followed by reduction with lithium aluminium hydride; 1-methyl-2-(3-hydroxypropyl)pyrrolidine by the formic acid/formaldehyde methylation of 2-(3-hydroxypropyl)pyrrolidine obtained by the action of lithium aluminium hydride on 5-(2-methoxycarbonylethyl) - 2 - pyrrolidone; and 1-methyl - 2 - (2 - chlorethyl)pyrrolidine by the action of thionyl chloride on 1-methyl-2-(2-hydroxyethyl)pyrrolidine.