A PROCESS FOR PREPARING THE KEY INTERMEDIATE OF APREMILAST, USING ENZYMATIC RESOLUTION OF THE RACEMIC AMINES

摘要

The invention relates to a preparation method of (S)-l-(3-ethoxy-4-methoxyphenyl)- 2-(methylsulfonyl)-ethyl-amine (S)-l, or its N-acyl derivatives of general formula (S)-2. The amine (S)-l is the key intermediate in the synthesis of (S)-{2-[l-(3-ethoxy-4- methoxyphenyi)-2-methyisulfonylethyl]-4-acetylaminoisoindolin-l ?3-dione, known as Apremilast. In this synthesis, the amine (S)-l, or its respective salts, are subjected to condensation with 3-acetamidophthalic anhydride 4, providing the desired product 3 (Scheme 1).