Tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate → tert-Butyl-3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxypropyl)azetidine-1-carboxylate

Participants

Reaction Steps

To a flask containing tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate (250 mg, 0.47 mmol, Intermediate 13: step b) was added THF (8 mL) to give a homogeneous solution. The solution was cooled in an ice-water bath and ethylmagnesium bromide (3 M in Et2O, 0.3 mL, 0.9 mmol) was introduced. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution and extracted with EtOAc, (4×30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness to afford a colorless gum. Chromatography on silica gel (5% EtOAc-DCM increasing to 1% MeOH-DCM) provided the title compound as a white amorphous solid. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=2.0 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.60 (dd, J=8.7, 2.1 Hz, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.1 Hz, 2H), 4.35 (s, 2H), 4.16-4.08 (m, 1H), 4.07 (s, 3H), 4.00 (t, J=8.5 Hz, 1H), 3.71-3.53 (m, 2H), 3.20-3.07 (m, 1H), 2.13 (s, 1H), 1.97-1.74 (m, 2H), 1.41 (s, 9H), 0.73 (t, J=7.4 Hz, 3H); MS (ESI): mass calcd. for C29H32ClF3N2O4, 564.2, m/z found 565.3 (M+H)+.

Provenance & Evidence