반응 #313619

반응 방정식

ethyl (dimethoxyphosphoryl)(fluoro)acetate

magnesium bromide

tert-butyl (3R)-3-[(3-chloro-5-formyl-2-pyridinyl)amino]-1-pyrrolidinecarboxylate

Et3N

→

tert-butyl (3R)-3-({3-chloro-5-[(1Z)-3-ethoxy-2-fluoro-3-oxo-1-propen-1-yl]-2-pyridinyl}amino)-1-pyrrolidinecarboxylate

수율 92.1%

용매

THF

AcOEt-H2O

THF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred at same condition for an hour
2. 2
   workup.STIRRINGwas stirred at 0-15° C. for 4 hours
3. 3
   세척the organic layer was washed with brine
4. 4
   건조dried over MgSO4
5. 5
   기타The solvent was evaporated in vacuo
6. 6
   기타the residue was chromatographed on silicagel
7. 7
   세척eluting with AcOEt-n-hexane (3:7)
8. 8
   workup.ADDITIONThe eluted fractions containing the desired product
9. 9
   기타were collected
10. 10
    기타evaporated in vacuo

실험 절차

To a mixture of ethyl (dimethoxyphosphoryl)(fluoro)acetate (2.08 g) and magnesium bromide (1.9 g) in THF (20 ml) was added dropwise to a Et3N (1.32 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 tert-butyl (3R)-3-[(3-chloro-5-formyl-2-pyridinyl)amino]-1-pyrrolidinecarboxylate (2.0 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 tert-butyl (3R)-3-({3-chloro-5-[(1Z)-3-ethoxy-2-fluoro-3-oxo-1-propen-1-yl]-2-pyridinyl}amino)-1-pyrrolidinecarboxylate (2.34 g)

출처