(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Participants

Reaction Steps

A solution of n-BuLi (2.5 M in hexanes, 4.6 mL, 11.5 mmol) was added drop-wise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (5.0 g, 11.6 mmol, Intermediate 47: step d) in dry THF (58 mL) in a dry ice-acetone bath. After 1 min, a solution of (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (2.6 g, 11.6 mmol, Intermediate 1: step b) in dry THF (58 mL) was added drop-wise via syringe. An additional 10 mL of THF was used to complete the quantitative addition. The reaction mixture was stirred for 5 minutes in the dry ice-acetone bath then placed into an ice-water bath. After 10 minutes, the ice-water bath was removed and the mixture was allowed to warm to ambient temperature. The reaction was quenched with saturated aqueous ammonium chloride and the mixture was partitioned between water and DCM. The layers were separated and the aqueous phase was further extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated. Crude product was purified by flash column chromatography (silica gel, 0-3% MeOH-DCM) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J=2.1 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.53 (dd, J=8.8, 2.1 Hz, 1H), 7.51-7.47 (m, 2H), 7.40-7.36 (m, 2H), 7.28-7.32 (m, 4H), 7.23-7.21 (m, 1H), 6.29 (d, J=1.2 Hz, 1H), 5.06 (s, 1H), 4.32 (s, 2H), 4.07 (s, 2H), 3.33 (s, 3H). MS m/e 572.0 (M+H).

Provenance & Evidence