Dimethylformamide → tert-Butyl 4-formyl-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Participants

Reaction Conditions

Reaction Steps

Carbon monoxide was bubbled through a solution of tert-butyl 4-iodo-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (1.36 g, 2.94 mmol) and 1,1′-bis-(diphenylphosphino)-ferrocene) palladium dichloride (0.241 g, 0.294 mmol) in DMF (20 mL) at 70° C. for 10 min. DIPEA (1.28 mL, 7.34 mmol) and trioctylsilane (2.64 mL, 5.87 mmol) were added. The reaction mixture was stirred at 70° C. under CO (balloon) overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc and washed with sat. aq. sodium bicarbonate solution, 10% aq. LiCl solution, and then sat. aq. sodium bicarbonate solution again. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting from 0-40% EtOAc/hexanes) to give the title compound (537 mg, 50%) as a yellow foam. 1H NMR (CDCl3, 1.5:1 mixture of amide rotamers) δ 10.19 (s, 0.5H), 10.14 (s, 0.5H), 8.17-8.13 (m, 1H), 8.03-7.98 (m, 2H), 7.26-7.10 (m, 4H), 5.00 (s, 1H), 4.33 (m, 1H), 4.09 (t, J=6 Hz, 1H), 3.45 (t, J=6 Hz, 1H), 3.04 (t, J=6 Hz, 1H), 2.80 (t, J=6 Hz, 1H), 1.61 (s, 9H); MS(ESI+) m/z 366.2 (M+H)+.

Provenance & Evidence