Thesis (M.Sc.)--Chulalongkorn University, 2011

To improve the azide route of the Roche synthesis of oseltamivir 9 using epoxide precursor 18 as a starting reagent. The synthesis consists of five reaction steps. The first reaction step is the ring opening reaction to provide the mixture of regioisomers of hydroxyl azide 19 and 43 in 88% yield. Both regioisomer could be converted through one-pot operation by in situ reduction with triphenylphosphine and ring closing to aziridine 20 followed by ring reopening with sodium azide to provide amino azide 21 in 50% yield from hydroxyl azide 9. The acetylation of amino azide 21 with acetyl chloride provided acetamido azide 22 in 97% yield. The reduction of acetamido azide 22 with triphenylphosphine was produced free base of oseltamivir 9 in 99%. The overall yield of these 4-steps process was 42%. The combined synthesis of steps 1-3 towards amino azide 21 could be achieved from epoxide 18 in 55% yield. Further combined synthesis of step 1-4 towards acetamido azide 22 could also be accomplished from epoxide 18 in 49% yield. Finally, the free base oseltamivir 9 could be obtained through one-pot procedure of step 1-5 from epoxide 18 in 18% yield.