| 摘要 |
A process for preparing the +E,uns d+EE -threo isomer of methylphenidate hydrochloride comprising converting +E,uns d,l+EE -threo methylphenidate hydrochloride to the free base form in a first step, resolving the free base prepared in the first step with (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate to obtain the phosphate salt enriched with the +E,uns d+EE -threo isomer of methylphenidate in a second step, basifying the phosphate salt to obtain the free base form of the +E,uns d+EE -threo isomer of methylphenidate in a third step, converting the free base to the hydrochloride salt form of the +E,uns d+EE -threo isomer of methylphenidate in high optical purity in a fourth step, and recrystallizing the hydrochloride salt form to obtain the desired +E,uns d+EE -threo isomer in a higher optical purity. An alternative embodiment relates to the preparation of the +E,uns d+EE -threo isomer of methylphenidate hydrochloride utilizing the hydrochloride salt form of the racemic mixture of threo-methylphenidate directly.
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