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

温度

7.5 °C

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)

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
5. customThe solvent was 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

ORDレコード

ord-a44a0ddc00184900931ef27b2e5c8914

出典データセット

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07557127B2