Tetrahydrofuran → (αR)-3-Chloro-α-methyl-6-isoquinolinemethanol

Participants

Reaction Conditions

Reaction Steps

Dichloro(p-cymene)ruthenium(II) dimer (3 mg, 0.005 mmol) and (1R,2R)-(−)-N-p-tosyl-1,2-diphenylethylenediamine (4.4 mg, 0.012 mmol) was suspended in degassed water (2 mL) and the mixture was degassed with nitrogen for 15 minutes. The mixture was stirred at 70° C. under nitrogen for 90 minutes. The resulting yellow solution was cooled to room temperature. 1-(3-Chloro-isoquinolin-6-yl)-ethanone (206 mg, 1 mmol), sodium formate (340 mg, 5 mmol) and degassed tetrahydrofuran (1 mL) were added and the reaction mixture was degassed with nitrogen for 5 minutes. The reaction mixture was vigorously stirred at 40° C. for 2.5 hours. The reaction mixture was cooled to room temperature and was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 4:1 to 2:1 to afford the title compound (193 mg, 92%) as a white solid. 1H NMR (300 MHz, CDCl3) δ1.60 (d, J=5.9 Hz, 3H), 2.14 (d, J=3.1 Hz, 1H), 5.08-5.16 (m, 1H), 7.63 (dd, J=8.6, 1.6 Hz, 1H), 7.72 (s, 1H), 7.77 (brs, 1H), 7.96 (d, J=8.6 Hz, 1H), 9.04 (s, 1H). LCMS (m/z) 208/210 [M+H], Tr=4.25 min.

Provenance & Evidence