(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 → (S)-ethyl 2-(2-(3-(6-(benzyloxy)-2,3-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 Conditions

Reaction Steps

To a suspension of (6-(benzyloxy)-2,3-difluorophenethyl)triphenylphosphonium, iodide salt (217 mg, 0.340 mmol) in THF (5 ml) at 0° C. was added n-Buli (0.213 ml, 0.340 mmol) and the resulting mixture was heated at 60° C. for 1 h. The mixture was then cooled to rt 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 (5 ml) was added dropwise and the mixture was stirred rt for 5 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-(6-(benzyloxy)-2,3-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 (114 mg, 0.114 mmol, 50% yield) as mixture of E and Z isomers. LCMS (M+H)=1001.8.

Provenance & Evidence