Patent GB-782935-A (GB)
Title: Heterocyclic acid diammonio esters
IPC: C07D295/088
Filed: 1955-03-25
Abstract: The invention comprises compounds of the formula <FORM:0782935/IV (a)/1> wherein R, R1, R11 and R111 are lower alky groups (containing 1 to 6 carbon atoms), n and m are integers from 1 to 6 inclusive and the group <FORM:0782935/IV (a)/2> represents a heterocyclic radical such as pyrrolidyl, morpholinyl, piperidyl and alkylsubstituted-piperidyl and the anions are nontoxic quaternary salt forming anions.  Such compounds are obtained by reacting a compound of the formula <FORM:0782935/IV (a)/3> with a quaternizing agent of the formula R11 anion or R111-anion or by reacting a compound of the formula <FORM:0782935/IV (a)/4> wherein X is chlorine, bromine or iodine, with a compound of the formula <FORM:0782935/IV (a)/5> Anions specified are chloride, bromide, iodide, picrate, sulphate, nitrate, citrate and bitartrate, and one may be exchanged for the other by, for example, treating the products with an anionexchange resin.  In examples: (1) 2-dimethylaminoethyl a - methyl - 1 - pyrrolidinopropionate is quaternated with methyl iodide, giving 2-trimethylammonioethyl 2-methyl-3-(1 - methylpyrrolidinio) propionate di-iodide.  Similarly obtained are (2) 2-trimethylammonioethyl 2 - methyl - 3 - (4 - methylmorpholinio) - propionate di-iodide; (5) 2 - (butyl - ethylmethylammonio) ethyl 3 - (1 - methylpyrrolidinio) propionate di-iodide; (6) 1-methyl-2-trimethylammonioethyl 3 - (1,4 - dimethylpiperidino) propionate di-iodide; (7) 2-trimethylammonioethyl 3 - (4 - methylmorpholinio) butyrate di-iodide; (8) 2-dimethylethylammonio) ethyl 3-(1-methyl-pyrrolidinio) butyrate di-iodide.  In further examples: (3) the product of Example (2) is converted to the dipicrate by reaction with picric acid; (4) 2-trimethylammoniobutyl 3 - iodopropionate iodide and 1-ethylpiperidine are reacted to form 2-trimethylammoniobutyl 3 - (1 - ethyl - piperidinio) propionate di-iodide.  Starting materials.  2-Dimethylaminoethyl methacrylate and pyrrolidine are reacted in the presence of N-phenyl-2-naphthylamine to give 2 - dimethylaminoethyl a  - methyl - 1 - pyrrolidinepropionate.  Similarly obtained is 2-dimethylaminoethyl a -methyl-4-morpholinepropionate.  Methyl iodide and 2-amino-1-butanol reacted in the presence of sodium hydroxide give 2-trimethylammoniobutanol iodide.  Reaction of this compound with 3-iodo-propionyl chloride gives 2 - trimethylammoniobutyl 3 - iodopropionate iodide. Butylethylamine and ethylene chlorohydrin are reacted to give 2-(butylethylamino)-ethanol.  Reaction of the latter with acrylyl chloride gives 2-(butylethylamino) ethyl acrylate, which on reaction with pyrrolidine gives 2-(butylethylamino) ethyl 1-pyrrolidine propionate.  Acrylyl chloride and 1-dimethylamino-2-propanol react to form 2-diethylamino-1-methylethyl acrylate, which is refluxed with pipecoline to form 2-dimethylamino-1-methylethyl 4-methyl1-piperidine-propionate. Crotonyl chloride and 2-dimethyl-aminoethanol are reacted to form 2-dimethyl-aminoethyl crotonate and this compound in the presence of N-phenyl-2-naphthylamine reacts with morpholine to form 2-dimethylaminoethyl b -methyl-4-morpholinepropionate.  Crotonyl chloride and 2-(ethylmethylamino)-ethanol react to form 2-(ethylmethylamino)-ethyl crotonate, reaction of which with pyrrolidine gives 2-(ethylmethylamino) ethyl b -methyl-1-pyrrolidinepropionate.