Efficient preparation of (S)‐2‐(3,5‐dimethylphenyl)pyrrolidine via a recycle process of resolution

Abstract ( S )‐2‐(3,5‐dimethylphenyl)pyrrolidine(( S )‐ 1 ), a key intermediate in the synthesis of aticaprant, was effectively prepared via a recycle process of resolution/racemization. The desired ( S )‐ 1 was obtained by resolution of its racemate with D ‐tartaric acid and some alkaline conditions were screened to racemize the undesired ( R )‐ 1 in the resolution mother liquor, and the best (in DMSO with KOH) was identified. Finally, the desired freebase ( S )‐ 1 was obtained in a yield of 63.6% with excellent enantioselectivity (98.7% ee) after three times of recycle process.