Patent GB-582535-A (GB)
Title: Manufacture of basic esters and basic amides of 1-phenyl-cycloalkyl-1-carboxylic acids, and the quaternary ammonium compounds thereof
IPC: A61K31/19
Filed: 1944-04-21
Abstract: Basic esters or basic amides are prepared by the interaction of a 1-phenyl-cycloalkyl-1-carboxylic acid or a reactive functional derivative thereof with an aliphatic amino-alcohol which is tertiarily substituted at the nitrogen, or with alkylene diamine containing a primary or secondary amino group, or by the interaction of the 1-phenyl-cycloalkyl-1-carboxylic acid or a salt thereof or the amide of this acid or a salt thereof or the amide of this acid aliphatic amino-alcohol which is tertiarily substituted at the nitrogen such as an ester with a hydrohalic or aryl sulphonic acid. If desired, an acid binding agent may be present during the condensation.  A further alternative comprises reacting a halogen alkyl ester or a halogen alkyl amide of a 1-phenyl-cycloalkyl-1-carboxylic acid with a secondary amine or with a tertiary amine.  In the latter case, the quaternary ammonium compound is obtained.  These quaternary compounds may also be obtained and are included in the invention, by treating the basic esters obtained by the processes indicated above with a quaternating agent.  In examples: (1) 1-phenyl-cyclopentyl-1-carboxylic acid chloride is reacted with diethylamino-ethanol in ether solution. Instead of the above acid, there may also be used substituted in the phenyl nucleus. Substituents mentioned include methoxy, ethoxy, chloro and bromo; (2) 1-phenyl-cyclohexyl-1-carboxylic acid is reacted with b -chloroethyldiethylamine, in the presence of potassium carbonate and ethyl acetate; (3) 1-(31 : 41-dimethyl-phenyl)-cyclopentyl-1-carboxylic acid chloride is reacted with diethylaminoethanol as in example (1). Alternative acids which may be reacted in the same manner include 1-(41-methylphenyl) - cyclohexyl - 1 - carboxylic acid and 1 - phenyl - 2 : 5 - dimethyl - cyclopentyl - 1 - carboxylic acid; (4) 1-phenyl cyclopentyl-1-carboxylic acid chloride is treated with N : N-diethyl-ethylene-diamine or N : N-diethyl-N1-ethyl-ethylene-diamine; (5) 1 - phenyl-cyclohexyl-1-carboxylic acid amide is treated with sodamide and then with b -chloroethyl-diethylamine.  The same compound may be obtained by heating 1-phenyl-cyclohexyl-1-carboxylic acid with 2-diethylamino-ethylamine; (6) 1-phenyl-cyclohexyl-1-carboxylic acid chloride is treated with ethylene chlorhydrin in the presence of pyridine.  The reaction product is then mixed with heating with piperidine; (7) 1-phenyl-cyclopentyl-1-carboxylic acid is treated with aminoethanol, the reaction product treated in chloroform solution with PCl5 and the chloro-ethylamide so p  formed heated with diethylamine; (8) 1-phenyl-cyclopentyl-1-carboxylic acid chloride is treated with g -dimethylaminopropanol.  Instead of acids unsubstituted in the phenyl nucleus, there may be used the corresponding 21 - methyl-, 31 - methyl-, 41 - methyl- and 31 : 41-dimethyl-compounds; (9) 1-phenyl-cyclobutyl-1-carboxylic acid chloride is reacted with diethylamino-ethanol.  Instead of an acid unsubstituted in the phenyl nucleus there may be used the 21-methyl-, 31-methyl-, 41-methyl-, 41-chloro- and 2-methoxy-compounds; (10) 1-phenyl-cyclopropyl-1-carboxylic acid chloride is reacted with diethylaminoethanol.  Instead of using the acid unsubstituted in the phenyl nucleus, there may be used acids substituted as listed in example (9); (11) 1-phenyl-cycloheptyl-1-carboxylic acid chloride is treated with diethylaminoethanol in ether solution.