Flow synthesis process for the production of oseltamivir

A flow synthesis process for producing a compound of the Formula 33 and its pharmaceutically acceptable salts,

• the process comprising the steps of:
• a) preparing ethyl shikimate of Formula 39
• by reacting shikimic acid with a reagent selected from the group consisting of (COCl)2, SOCl2, benzene sulphonic acid (BSA), p-toluene sulphonic acid (PTSA), and Amberlyst 15,
• b) reacting the ethyl shikimate of Formula 39 with mesyl chloride in the presence of a base selected from the group consisting of trimethyl amine (TEA), 1,8-diazabicyclo(5.4.0) undec-7-ene (DBU), imidazole, and trihexyl amine (THA) to produce the O-trimesylate of Formula 40, wherein the base is present at a concentration of about 8 to about 20 molar equivalents relative to ethyl shikimate,
• c) reacting the O-trimesylate of Formula 40 in an azidation reaction with an appropriate azidating agent to produce the azide of Formula 41
• d) reacting the azide of Formula 41 in an aziridation reaction with a trialkyl phosphite to produce the aziridine of Formula 42
• e) reacting the aziridine of Formula 42 with 3-pentanol in the presence of a Lewis acid catalyst to produce the 3-pentyl ether of Formula 43
• f) reacting the 3-pentyl ether of Formula 43 in an acetylation reaction with H2SO4, followed by Ac2O in the presence of a suitable base to produce the acetamide of Formula 44
• g) reacting the acetamide of Formula 44 in an azidation reaction with an appropriate azidating reagent produce the azide of Formula 32
• and
• h) reacting the azide of Formula 32 by mixing the azide with CoCl2, and reacting the mixture with NaBH4 to produce the compound of Formula 33.