Process for the preparation of (2R,3S)-3-phenylisoserine methyl ester acetate salt
A process for the enantioselective preparation of (2R,3S)-3-phenylisoserine methyl ester acetate salt of formula (I) which is an useful building block for the synthesis of taxane derivatives. The process involves the resolution of racemic threo-phenylisoserine amide and its conversion into (I).
1. A process for the preparation of (2R,3S)-3-phenylisoserine methyl ester acetate salt (I)
which comprises the following steps:
a) treatment of racemic threo 3-phenylisoserine amide (VI)
with an enantiomerically pure organic acid to provide a corresponding acid salt of (2R,3S)-3-phenylisoserine amide;
b) treatment of the acid salt of (2R,3S)-3-phenylisoserine amide with a strong inorganic acid in a protic solvent to provide a (2R,3S)-3-phenylisoserine amide inorganic acid salt;
c) treatment of the (2R,3S)-3-phenylisoserine amide inorganic acid salt with hydrochloric acid in a protic solvent followed by treatment with acetic acid to crystallise (2R,3S)-3-phenylisoserine methyl ester acetate salt (I).
2. A process according to claim 1 wherein the solvent is ethanol.
3. A process according to claim 1 wherein step b) is carried out using sulfuric or hydrochloric acid in ethanol as solvent.
4. A process according to claim 1 wherein the protic solvent of step c) is methanol and (2R,3S)-3-phenylisoserine methyl ester acetate salt (I) is crystallized from a mixture of ethyl acetate and heptane.