(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanone → 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(2,6-dimethylpyridin-3-yl)ethanol

Participants

Reaction Steps

To a flask containing (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanone (220 mg, 0.45 mmol, Intermediate 10: step b) was added THF (15 mL). The solution was cooled in a dry ice bath and then MeLi (1.6 M in Et2O, 0.33 mL, 0.53 mmol) was introduced. After 40 minutes, the reaction was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (4×30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness to afford an amber gum. Chromatography on silica gel (3% MeOH-DCM increasing to 5% MeOH) provided the title compound as a white amorphous solid. 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J=2.0 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.45-7.35 (m, 3H), 7.07 (d, J=8.0 Hz, 1H), 4.34 (s, 2H), 4.06 (s, 3H), 2.54 (s, 3H), 2.24 (s, 1H), 2.17 (s, 3H), 2.01 (s, 3H); MS (ESI): mass calcd. for C27H24ClF3N2O2, 500.2, m/z found 501.1 [M+H]+. 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(2,6-dimethylpyridin-3-yl)ethanol was purified by chiral SFC (Stationary phase: Chiracel OD column (50×250 mm, 5 micron), Mobile phase: 12% EtOH-hexane with 0.2% Et3N), to give 2 enantiomers. The first eluting enantiomer was Example 13b and the second eluting enantiomer was Example 13c.

Provenance & Evidence