Method of preparing amides of n-alkyl piperidine mono-carboxylic acid and n-alkyl pyrrolidine -a-monocarboxylic acid

摘要

Amides of the general formul FORM:0775750/IV(b)/1 and FORM:0775750/IV(b)/2 wherein R1 is an alkyl group, R2 an alkyl group of 1-5 carbon atoms or chlorine, R3 a hydrogen atom, an alkyl group of 1-5 carbon atoms, an alkoxy or a hydroxy group, and R4 a hydrogen atom, chlorine, an alkyl group of 1-5 carbon atoms or an alkoxy group, or in which R2, R3 and R4 are all hydrogen, are prepared by reacting an appropriately substituted aniline magnesium halide with the appropriate pyridine, piperidine, pyrrole or pyrrolidine monocarboxylic acid ester, which may or may not be N-alkylated, hydrolysing the reaction product and, where required, hydrogenating the heterocyclic ring and alkylating the nitrogen atom thereof. In the examples: (1) ethyl magnesium bromide and 2 : 6-dimethylaniline give 2 : 6-dimethylaniline magnesium bromide, this is refluxed with N-methylpipecolic acid ethyl ester and the product on hydrolysis with dilute Hcl gives N-methylpipecolic acid 2 : 6-dimethylanilide; (2) nipecotic acid 2-ethylanilide, prepared as in example (1), is alkylated with isopropyl bromide to give N-isopropylnipecotic acid 2-ethylanilide; (3) isonicotinic acid anilide, prepared as in example (1), is catalytically hydrogenated and the product is alkylated with dimethyl sulphate to give N-methylisonipecotic acid anilide; (4) 2-chloro-6-methylaniline magnesium bromide and N-n-butylpyrrolidine a -carboxylic acid ester give N-n-butylpyrrolidine a -carboxylic acid 2-chloro-6-methylanilide; (5) pipecolinyl - 2 : 4 : 6 - trimethylanilide, prepared as in example (1), is alkylated with diethyl sulphate to give N-ethylpipecolinyl-2 : 4 : 6-trimethylanilide; (6) 2 : 6 - dimethyl - 4 - butoxyaniline magnesium bromide and N-methylpipecolinic acid ethyl ester give N-methylpipecolinyl - 2 : 6 - dimethyl - 4 - butoxyanilide. Specifications 770,129 and 772,807 are referred to.