Process for preparing 1-(p-acetylphenyl)-2-(2,2-dichloroacetamido)-1,3-propanediol

摘要

1 - (p - Acetylphenyl) - 2 - (2,2 - dichloro-acetamido) - 1,3 - propanediol, in D,L - erythro and threo forms is made by reducing an ester of b -(p-acetylphenyl)-serine or its hydrochloride, in which the acetyl group is protected by an ethylenedioxy residue, forming a cyclic acetal, to give the corresponding protected 3-p-acetylphenyl - 2 - amino - propane - 1,3 - diol and acylating the product with a dichloroacetylating agent, the protecting group being previously or subsequently removed. Suitably, a high threo-content or high erythro-content D,L - b - [p - (2 - methyl - 1,3 - dioxolan - 2 - yl) phenyl] serine ethyl ester hydrochloride prepared according to Specification 1,117,617 is reduced with lithium aluminium hydride, the resulting 1 - [p - (2 - methyl - 1,3 - dioxolan - 2 - yl)phenyl] - 2 - amino - 1,3 - propanediol is reacted with methyl dichloroacetate and the N-dichloroacetyl compound obtained is hydrolysed with dilute hydrochloric acid to remove the ethylenedioxy residue. p - (2 - Methyl - 1,3 - dioxolan - 2 - yl) phenyl-serine ethyl ester hydrochloride is made by (A) reacting p-acetylbenzonitrile with ethylene glycol to give p-(2-methyl-1,3-dioxolan-2-yl) benzonitrile, treating with lithium aluminium hydride or lithium triethoxy aluminium hydride to form p-(2-methyl-1,3-dioxolan-2-yl) benzaldehyde, condensing with glycine ethyl ester to give N - [p - (2 - methyl - 1,3 - dioxolan - 2 - yl) benzylidene] - 3 - [p - (2 - methyl - 1,3 - dioxolan- 2 - yl) phenyl] - serine ethyl ester and hydrolysing this with aqueous HCl (B) condensing p - (2 - methyl - 1,3 - dioxolan - 2 - yl) benzaldehyde with glycine in the presence of a base and esterifying the resulting p-(2-methyl-1,3-dioxolan - 2 - yl) phenylserine or (C) reacting p-acetylbenzaldehyde with glycine ethyl ester and reacting the product with glycol.