The present invention provides a process for the preparation of threo-methylphenidate hydrochloride. According to a preferred embodiment, the process comprises the following steps:
(a) contacting 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula
1
wherein Ar denotes an aryl group, where the aryl group may be substituted by a C
1
-C
6
alkyl, halo or nitro group;
with an inorganic base in the presence of a water immiscible organic solvent and a phase transfer catalyst to obtain (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula:
2
(b) reacting the (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one prepared in step (a) with a solution of hydrogen chloride in methanol to obtain threo-enriched methylphenidate hydrochloride;
(c) crystallizing the threo-enriched methylphenidate hydrochloride prepared in step (b) to give the desired threo-methylphenidate hydrochloride. Preferably, the threo-methylphenidate hydrochloride produced by the process of the present invention contains no more than 1% of the erythro-isomer.
本发明提供了一种制备
左旋甲基苯丙胺盐酸盐的方法。根据一个优选实施例,该方法包括以下步骤:(a)将式1中Ar代表芳基的1-(苯基甘氧基基)
哌啶芳磺酰
肼与一种
无机碱在
水不相溶有机溶剂和相转移催化剂的存在下接触,以获得(R*,R*)-富集的7-苯基-1-
氮杂双环[4.2.0]辛酮的化合物:2(b)将步骤(a)中制备的(R*,R*)-富集的7-苯基-1-
氮杂双环[4.2.0]辛酮与
甲醇中的
盐酸氢溶液反应,以获得左旋富集的甲基苯
丙胺盐酸盐;(c)结晶步骤(b)中制备的左旋富集的甲基苯
丙胺盐酸盐,以得到所需的
左旋甲基苯丙胺盐酸盐。最好,本发明的方法生产的
左旋甲基苯丙胺盐酸盐不含多于1%的对映异构体。