A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid

New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (−)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 7 successfully served as the key steps.