Formic Acid → 1-(Azetidin-3-yl)-1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)prop-2-yn-1-ol

Participants

Reaction Conditions

Reaction Steps

To a flask containing tert-butyl 3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxyprop-2-yn-1-yl)azetidine-1-carboxylate (165 mg, 0.29 mmol, Example 8) was added formic acid (5 mL, 132.5 mmol). The solution was cooled to 0° C. and 6 N aqueous HCl (50 μL, 0.3 mmol) was added. The mixture was stirred at 0° C. for 30 minutes then allowed to warm to room temperature. After 60 minutes, the reaction mixture was quenched with MeOH (10 mL) and stirred for 15 minutes and then concentrated. The residue was passed through a short column of silica gel (5% MeOH-DCM increasing to 10% 2 M NH3 in MeOH) which afforded the title compound as a light amber solid. 1H NMR (400 MHz, CD3OD) δ 8.44 (d, J=2.0 Hz, 1H), 8.01-7.72 (m, 3H), 7.53 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 4.43-4.25 (m, 3H), 4.22-4.09 (m, 2H), 4.06 (d, J=2.2 Hz, 3H), 3.88 (t, J=9.7 Hz, 1H), 3.49-3.36 (m, 1H), 3.36 (d, J=1.9 Hz, 1H). MS (ESI): mass calcd. for C24H20ClF3N2O2, 460.1; m/z found 460.9 [M+H]+.

Provenance & Evidence