2 - chloro - 4 - n - (amp; amp; beta; - diäthylaminoäthyl) - aminocarbonyl - 5 - methoxybenzoesäurederivate and methods for their manufacture and further implementation of metoclopramide

摘要

PURPOSE:The thermal rearrangement reaction of 2-chloro-4-N-(beta-diethylamino- ethyl)aminocarbonyl-5-methoxybenzhydroxamic acid or its metal salt is effected to produce title compound useful as an anti-emetic in high yield. CONSTITUTION:A compound of formula II or III (M is alkali or alkaline earth metal) is rearranged by heating up to 150-250 deg.C in the presence of an inert solvent as toluene, etc., to produce methoclopramide of formula I. The starting compound, one of formula II or III, is prepared by convwrting a compound of formula IV in the presence of a reagent of hydroxylamine, etc., to a hydroxamic acid or adding an alkali metal hydroxide as sodium hydroxide to the reaction system and effecting the reaction. EFFECT:The reaction goes with high selectivity and the product can be readily separated and purified, thus being-purity and low in cost. USE:An agent for improving digestive function.