Patent GB-661499-A (GB)
Title: Amino acetic acid esters
IPC: C07D295/145
Filed: 1949-05-30
Abstract: Phenyl aminoacetic acid ester compounds having the formula <FORM:0661499/IV (b)/1> are prepared by reacting a phenyl haloacetic acid ester of formula <FORM:0661499/IV (b)/2> with a heterocyclic nitrogen compound containing a secondary ring nitrogen atom where R is an alkyl or aralkyl radical, the alkyl radical containing from one to six carbon atoms; R1 and R2 are the same or different and represent hydrogen, halogen, alkyl or alkoxy radicals, the alkyl and alkoxy radicals containing from one to six carbon atoms; R3 is a residue of a heterocyclic nitrogen compound bound to the aliphatic carbon atom of the phenyl aminoacetic acid ester through a secondary ring nitrogen atom and X is a chlorine or bromine atom.  The reaction is carried out at a temperature between 10 DEG  and 150 DEG  C. Phenyl aminoacetic acid esters may also be prepared by 2- or 3-step processes starting from a phenyl haloacetyl halide or a phenyl acetyl halide respectively, the last step in each case being the reaction of a phenyl haloacetic acid ester with a heterocyclic nitrogen compound containing a secondary ring nitrogen compound.  The reactions are represented as follows: <FORM:0661499/IV (b)/3> where X and X1 are the same or different and represent chlorine or bromine atoms.  The halogenation represented by step (a) is carried out in the presence of light in the presence, if required, of an inert organic solvent such as carbon tetrachloride.  The esterification process represented by (b) is carried out in the usual manner in the presence or absence or an inert organic diluent such as ether, dioxane, petroleum ether, benzene, toluene and xylene.  Step (c) is carried out after the removal of halogen halide from the mixture.  Suitable heterocyclic nitrogen compounds are pyrrolidine, piperidine, morpholine, thiomorpholine, tetrahydroquinoline and lower alkyl carbon-substituted derivatives thereof.  The phenyl amino acetic acid esters produced form acid addition salts with inorganic and organic acids such as hydrochloric, hydrobromic, hydriodic, sulphuric, sulphamic, tartaric, oxalic, benzoic, citric, picric and acetic acids.  In the examples (a) ethyl phenyl-N-piperidylacetate is prepared by (i) reacting piperidine with ethyl phenyl bromoacetate, (ii) brominating phenyl acetyl chloride, treating the resulting compound with ethyl alcohol and then with piperidine; (b) methyl phenyl-N-piperidylacetate is prepared by reacting phenyl bromoacetyl chloride with methyl alcohol and treating the methyl phenyl bromoacetate so formed with piperidine; the hydrochloride salt can be precipitated by the addition of hydrochloric acid; (c) n-propyl phenyl-N-piperidylacetate is prepared by treating phenyl bromoacetyl chloride with n-propyl alcohol and treating the n-propyl phenyl bromoacetate so formed with piperidine; (d) isopropyl phenyl-N-piperidyl acetate is prepared by reacting piperidine with isopropyl phenyl bromo acetate; (e) n-butyl phenyl-N-piperidylacetate is prepared by reacting phenyl bromoacetate so formed with piperidine; (f) isobutyl phenyl-N-piperidylacetate is prepared by reacting bromoacetyl chloride with isobutyl alcohol and treating the resulting compound with piperidine; (g) ethyl phenyl-N-(2-methylpiperidyl)-acetate is prepared by reacting ethyl phenyl bromoacetate with 2-methyl piperidine; (h) ethyl phenyl-N-morpholinylacetate is prepared by treating ethyl phenyl bromoacetate with morpholine; (j) ethyl phenyl-N-tetrahydroquinolylacetate is prepared by treating ethyl phenyl bromoacetate with tetrahydroquinoline; (k) isopropyl-p-tolyl-N-piperidylacetate is prepared by treating isopropyl p-tolyl bromoacetate with piperidine; (1) ethyl - o - anisyl - N - (2,6 - dimethylpiperidyl)-acetate is prepared by treating ethyl o-anisyl bromoacetate with 2,6-dimethylpiperidine; (m) n - propyl - m - chlorophenyl - N - (3-methylpiperidyl)-acetate is prepared by treating n-propyl-m-chlorophenyl bromoacetate with 3-methylpiperidine; (n) ethyl phenyl-N-pyrrolidylacetate is prepared by treating ethyl phenyl bromoacetate with pyrrolidine; (o) isopropyl 3,4 - dimethylphenyl - N - (21,51 - dimethylpyrrolidyl)-acetate is prepared by treating isopropyl 3,4 - dimethylphenyl bromoacetate with 2,5-dimethylpyrrolidine; (p) benzyl 2-methyl - 5 - bromophenyl - N - (41 - ethylpiperidyl)-acetate is prepared by treating 2-methyl-5-bromophenyl bromoacetate with 4-ethyl piperidine. Other new phenyl acetic acid esters which can be prepared are isopropyl 4-chlorophenyl - N - morpholinylacetate, benzyl phenyl - N - (3 - ethylmorpholinyl) - acetate, n - propyl - 3 - ethylphenyl - N - (21 - methyltetrahydroquinolyl) - acetate, methyl 3-methoxyphenyl - N - (21 - methylmorpholinyl)-acetate, sec. - butyl 3,5 - dichlorophenyl - N-piperidylacetate, phenethyl 4-ethoxyphenyl-N-pyrrolidylacetate, ethyl 2 - chlorophenyl - N-piperidyl acetate, ethyl 3,4-dichlorophenyl-N-piperidyl acetate, ethyl 4-methoxy-phenyl-N-piperidylacetate and ethyl 3-methylphenyl-N-piperidylacetate.