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

온도

4 °C

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).

1. stirringThe reaction mixture was stirred at same temperature for 2.5 hrs
2. washThe separated organic layer was washed with water
3. dry with materialdried over magnesium sulfate
4. customevaporated in vacuo
5. customThe residue was purified by column chromatography on silica gel using
6. additiona mixture of AcOEt and hexane (1:2 v/v) as an eluant
7. additionThe eluted fractions containing the desired product
8. customwere collected
9. customevaporated in vacuo

ORD 기록

ord-7c88d9cee2534b6ca1e1e09d580164f5

출처 데이터셋

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07557127B2