Novel Bis-(p-Chloro-Phenoxy)-Acetic Acid Esters, the Preparation thereof and Compositions Containing them

摘要

1,187,501. Bis - (p - chlorophenoxy) - acetic acid esters. SANDOZ Ltd. 24 April, 1967 [12 May, 1966; 29 July, 1966; 5 Dec., 1966; 1 Feb., 1967], No. 18833/67. Heading C2C. Novel bis-(p-chlorophenoxy)-acetic acid esters of the general formula wherein R is a radical of the general formula -(CH 2 ) n R 1 , or a 2-dimethylamino-2-methyl-propyl-1 radical ; R 1 is a pyrrolidino, piperidino, morpholino, dialkylamino, anilino or a N-alkyl-anilino radical, or a radical of the formula in which " alkyl " means C 1 -C 4 alkyl; R 2 is C 1 -C 4 alkyl, a phenyl radical, a C 7 -C 10 phenylalkyl radical, or a propargyl or #-(p-chlorophenoxy)-ethyl radical; and n is a whole number from 2 to 4, with the proviso that when R is a 4-piperidyl radical, R 2 is not a methyl group, and acid addition salts and quaternary ammonium derivatives thereof are prepared (a) by reaction of a bis-(p-chlorophenoxy)- acetic acid alkyl ester of the general formula wherein R11 is C 1 -C 4 alkyl, with an alcohol of the general formula ROH; (b) by reaction of a bis.(p-chlorophenoxy)-malonic acid dialkyl ester of the general formula with an alcohol of the general formula ROH at a temperature of at least 110‹ C.; or (c) by reaction of a bis-(p-chlorophenoxy)-acetyl halide of the general formula wherein X is chlorine or bromine with an alcohol of the general formula ROH or an alcoholate of the general formula ROMe, in which Me is an alkali metal; followed optionally by conversion to an acid addition salt or quaternary ammonium derivative of the product. Bis-(p-chlorophenoxy)-acetic acid methyl ester is prepared by reaction of sodium p-chlorophenolate with methyl dichloroacetate. 4- Hydroxy - 1 - [# - (p - chlorophenoxy) - ethyl]- piperidine is prepared by reaction of 4-hydroxypiperidine with #-(p-chlorophenoxy)-ethyl bromide. 4 - Hydroxy - 1 - propargyl - piperidine is prepared by reaction of 4-hydroxy-piperidine with propargyl bromide. Pharmaceutical compositions having hypocholesteremic and hypolipemic effects contain, as active ingredient, a bis-(p-chlorophenoxy)- acetic acid ester of the first general formula above and a physiologically acceptable, inert carrier, and may be administered orally.