Tetramethyltin → HCID 68668567, compound

Participants

Reaction Conditions

Reaction Steps

Bis(triphenylphosphine)palladium(II)dichloride (94 mg, 0.13 mmol) was added to a solution of 3-(5-bromo-4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1H-imidazol-2-yl)-1,1-difluoro-2-[4-(1H-pyrazol-1-yl)phenyl]propan-2-ol (202 mg, 0.45 mmol), tetramethyltin (319 mg, 1.78 mmol), lithium chloride (151 mg, 3.57 mmol), and triphenylphosphine (47 mg, 0.18 mmol) in degassed N,N-dimethylformamide (10 mL) at ambient temperature. The solution was stirred at 120° C. for 2 hr. The solution was cooled to ambient temperature and saturated aqueous potassium fluoride (10 mL) was added. The mixture was stirred for 1 hr at ambient temperature. Diethyl ether and water was added and the layers were separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with brine, dried (MgSO4), and concentrated in vacuo. Chromatography over C-18 silica eluting with 10-100% acetonitrile/water afforded the title compound as a white solid. 1H NMR (500 MHz, CD3OD) δ 8.22 (d, J=2.5 Hz, 1H), 7.77-7.72 (m, 2H), 7.62-7.51 (m, 3H), 6.53 (t, J=2.0 Hz, 1H), 6.14 (t, J=55.2 Hz, 1H), 3.57-3.48 (m, 2H), 2.90 (dd, J=15.7, 60.7 Hz, 2H), 2.16 (s, 3H), 0.86 (dd, J=5.0, 5.0 Hz, 2H), 0.52 (dd, J=9.5, 33.0 Hz, 2H). Individual enantiomer (E1 or E2) was obtained by HPLC separation on a chiral column.

Provenance & Evidence