反应详情

温度

7.5 °C

To a mixture of ethyl (dimethoxyphosphoryl)(fluoro)acetate (1.46 g) and magnesium bromide (1.33 g) in THF (20 ml) was added dropwise to a Et3N (0.92 ml) with stirring at 0-15° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at same condition for an hour. A solution of 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde (1.36 g) in THF (10 ml) solution was added the above mixture and resultant mixture was stirred at 0-15° C. for 4 hours. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4— The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-n-hexane (3:7). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate (1.42 g).

1. stirringthe reaction mixture was stirred at same condition for an hour
2. stirringwas stirred at 0-15° C. for 4 hours
3. washthe organic layer was washed with brine
4. dry with materialdried over MgSO4— The solvent
5. customwas evaporated in vacuo
6. customthe residue was chromatographed on silicagel
7. washeluting with AcOEt-n-hexane (3:7)
8. additionThe eluted fractions containing the desired product
9. customwere collected
10. customevaporated in vacuo