반응 #313624

반응 방정식

ethyl (dimethoxyphosphoryl)(fluoro)acetate

magnesium bromide

6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde

Et3N

→

ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate

수율 81.6%

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— The solvent
5. 5
   기타was 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 (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).

출처