反应详情

温度

-78 °C

5-Benzyloxycarbonylamino-2-(4-ethyl-3-oxopiperazin-1-yl)fluorobenzene (3.25 g) was dissolved in dry THF (100 ml) under argon. The solution was cooled to -78° C., and treated with a solution of n-butyllithium (1.6 M in hexane, 6.02 ml), keeping the temperature below -60° C. 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU, 10 ml) was added to the resulting mixture to facilitate stirring, and (R)-glycidylbutyrate (1.29 ml) added. Stirring was continued at -78° C. for 30 minutes, before allowing the temperature to rise to ambient over 16 hours. Sodium bicarbonate solution (50 ml) was added, followed by sufficient ethyl acetate to form two layers. The organic layer was separated, washed twice with water, dried (MgSO4) and evaporated. The residue was chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 6% methanol in dichloromethane. Relevant fractions were combined and evaporated to give (5R)-3-(3-fluoro-4-{4-ethyl-3-oxopiperazine-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (990 mg).

1. customthe temperature below -60° C
2. stirringStirring
3. waitto ambient over 16 hours
4. customto form two layers
5. customThe organic layer was separated
6. washwashed twice with water
7. dry with materialdried (MgSO4)
8. customevaporated
9. customThe residue was chromatographed on silica
10. temperaturea gradient increasing in polarity from 0 to 6% methanol in dichloromethane
11. customevaporated