Sodium hydride → (S)-ethyl 2-(2-(3-(2-(benzyloxy)-3,5-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

Participants

Reaction Steps

To a suspension of (2-(benzyloxy)-3,5-difluorophenethyl)triphenylphosphonium, iodide salt (330 mg, 0.519 mmol) in THF (4 ml) at 0° C. was added NaH (21.27 mg, 0.532 mmol) and the resulting mixture was stirred at rt for 45 min. The mixture was cooled to 0° C. rd (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 (200 mg, 0.259 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)-3,5-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, 73% yield) as mixture of E and Z isomers. LCMS (M+H)=1002.0.

Provenance & Evidence