Water → Oseltamivir

Participants

Reaction Steps

A stirred solution of oseltamivir phosphonate 100 mg, in 50 mL DCM was treated with 50 mL water, Na2CO3 (60 mg). The white solution was stirred over a period of 45 minutes at room temperature. The combined aqueous and organic layers were extracted with dichloro methane (100 mL) and the organic phase was dried over Na2SO4 and the combined organic phase was evaporated in a rotary evaporator to yield the product oseltamivir as a liquid. This oseltamivir was used without further purification in the next step. Oseltamivir amine was coupled with Fmoc-PEG-acid (16 atoms) in the presence of EDC, HOBt and DIPEA in DCM. The solution was stirred over a period of 16 h at room temperature. The crude product was purified by silica column chromatography using a 8:2 mixture of DCM and hexane. The combined fractions were evaporated and dried on a rotary evaporator to obtain the product as a yellow oil. A solution of 20% piperidine in dichloromethane was added to the above a yellow oil and stirred for 30 min. The crude product was purified by preparative RP-HPLC using aqueous CH3CN, then freeze-dried to yield the desired compound as a pale yellow resin.

Provenance & Evidence