Diethyl Ether → tert-butyl [4-(2-{(1S,2R)-2-[1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2,6-difluorophenyl]acetate

Participants

Reaction Conditions

Reaction Steps

A 0.5 M solution of 2-(tert-butyloxy)-2-oxoethylzinc chloride in Et2O (43 mL, 21.2 mmol) was added to a mixture of 2-(4-((1R,2S)-2-(2-(4-bromo-3,5-difluorophenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-ethoxypyrimidine (3.4 g, 7.05 mmol), Pd2(dba)3 (0.484 g, 0.529 mmol), and X-PHOS (504 mg, 1.06 mmol) in anhydrous THF (10 mL). The mixture was stirred and heated at 65° C. overnight. The mixture was cooled to rt and filtered through celite, washing the filtercake with excess EtOAc. The volatiles were removed and the residue was purified by column chromatography on silica gel (KP-Sil 100 g SNAP column, Biotage system) eluting with 5-40% EtOAc:hexanes over 12 CV to afford the title compound. LC/MS (m/z): 518 (M+H)+.

Provenance & Evidence