IMPROVED PROCESS FOR THE MANUFACTURE OF R-6-HYDROXY-8-[1-HYDROXY-2-[2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYLAMINOETHYL]-2H-1,4-BENZOXAZIN-3(4H)-ONE HYDROCHLORIDE

• Main Authors: DALMASES BARJOAN PERE, HUGUET CLOTET JUAN, CAPDEVILA URBANEJA ENRIC
• Format: Patent
• Language: Chinese; English
• Published: 09.08.2019
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The present invention provides an improved process for the manufacture (R)-6- hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethyl-ethylamino-ethyl]-2H-1,4- benzoxazin-3(4H)-one, in high purity and high yield, through the use of 1,1-dimethyl-2- (4-methoxyphenyl)ethyl amine L-tartrate salt, 1,1-dimethyl-2-(4-methoxyphenyl)ethyl amine maletate salt or the camphor sulfonate salt of intermediate (4). The invention also relates to sais salts, to processes for preparing them and to their use for the manufacture of (R)-6-hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethyl- ethylamino-ethyl]-2H-1,4-benzoxazin-3(4H)-one or a pharmaceutically acceptable salt thereof. 本发明提供了用于通过使用1，1-二甲基-2-(4-甲氧基苯基)乙基胺L-酒石酸盐、1，1-二甲基-2-(4-甲氧基苯基)乙基胺马来酸盐或中间体(4)的樟脑磺酸盐，以高纯度和高产率制备(R)-6-羟基-8-[1-羟基-2-[2-(4-甲氧基苯基)-1，1-二甲基-乙基氨基-乙基]-2H-1，4-苯并嗪-3(4H)-酮的改进方法。本发明还涉及所述盐、用于制备它们的方法、及其用于制备(R)-6-羟基-8-[1-羟基-2-[2-(4-甲氧基苯基)-1，1-二甲基-乙基氨基-乙基]-2H-1，4-苯并嗪-3(4H)-酮或其可药用盐的用途。