Proxen - Naproxen

Tartaric acid has been used as a chiral auxiliary in a patented route to (S)-na-proxen (11) (Scheme 1) [40-44]. In initial studies, the acetal 12 was used to allow stereoselective bromination that resulted in a 91 9 ratio of the (7 7 5)- and (7 /lR)-bromo derivatives (13 and 14). The bromo acetal diesters could be completely separated. Debromination of 13 followed by acid hydrolysis led to formation of (S)-naproxen in 80% yield, > 99% enantiomeric excess (ee), and recovery of the auxiliary. Conversely, debromination and hydrolysis of 14 gave only 12% yield of (A)-naproxen and 86% ee. In this case, the hydroxy acetal 15 was the major product (68%). However, the auxiliary was recovered in enantiomerically pure form. 

---