반응 #313567

반응 방정식

ethyl (dimethoxyphosphoryl)(fluoro)acetate

MgBr2

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

HCl

→

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

용매

THF

Et3N

THF

AcOEt

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction mixture was stirred at same temperature for 2.5 hrs
2. 2
   세척The separated organic layer was washed with water
3. 3
   건조dried over magnesium sulfate
4. 4
   기타evaporated in vacuo
5. 5
   기타The residue was purified by column chromatography on silica gel using
6. 6
   workup.ADDITIONa mixture of AcOEt and hexane (1:2 v/v) as an eluant
7. 7
   workup.ADDITIONThe eluted fractions containing the desired product
8. 8
   기타were collected
9. 9
   기타evaporated in vacuo

실험 절차

The mixture of ethyl (dimethoxyphosphoryl)(fluoro)acetate (2.51 mL), MgBr2 (2.73 g), Et3N (1.89 mL) in THF (45 mL) was stirred at 3-5° C. for 1 hr and to the mixture was dropwise added a solution of tert-butyl (3R)-3-[(3-chloro-5-formyl-2-pyridinyl)amino]-1-piperidinecarboxylate (3.0 g) in THF (21 mL) at 3-5° C. The reaction mixture was stirred at same temperature for 2.5 hrs. The reaction mixture was poured into a mixture of AcOEt and ice-water and the mixture was adjusted to pH 3.5 with 1N-HCl. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel using a mixture of AcOEt and hexane (1:2 v/v) as an eluant. 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-piperidinecarboxylate (3.38 g).

출처