反应详情

To a suspension of (2-(benzyloxy)-4,5-difluorophenethyl)triphenylphosphonium iodide salt (289 mg, 0.454 mmol) in THF (4 ml) at 0° C. was added NaH (18.61 mg, 0.465 mmol) and the resulting mixture was stirred at rt for 45 min. The mixture was cooled to 0° C. and (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-formyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (175 mg, 0.227 mmol) dissolved in THF (4 ml) was added dropwise and the mixture was stirred at 0° C. for 1 h then warmed to rt and stirred 2 h. The reaction was quenched with water and the product was extracted with EtOAc. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage; 0%-30% EtOAc/hexane) to afford (S)-ethyl 2-(2-(3-(2-(benzyloxy)-4,5-difluorophenyl)prop-1-en-1-yl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (190 mg, 0.190 mmol, 84% yield) as mixture of E and Z isomers. LCMS (M+H)=1002.0.

1. temperatureThe mixture was cooled to 0° C.
2. additionwas added dropwise
3. stirringthe mixture was stirred at 0° C. for 1 h
4. temperaturethen warmed to rt
5. stirringstirred 2 h
6. customThe reaction was quenched with water
7. extractionthe product was extracted with EtOAc
8. washThe organic phase was washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by flash chromatography (Biotage; 0%-30% EtOAc/hexane)