Chlorodifluoromethane → 4-(Difluoromethoxy)-1-piperidinecarboxaldehyde

Participants

Reaction Steps

4-hydroxypiperidine-1-carbaldehyde (10.8 g, 83.62 mmol) was dissolved in tetrahydrofuran (150 mL). To this was added sodium hydride (5.22 g, 108.70 mmol) and the reaction was stirred for 30 minutes. 15-crown-5 (9.21 g, 41.81 mmol) was added and the reaction was stirred for a further 30 minutes before the slow addition of chlorodifluoromethane (8.68 g, 100.34 mmol), after the addition the reaction was stirred for 30 minutes. The reaction mixture was quenched with saturated brine (75 mL), extracted with diethyl ether (3×100 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a yellow liquid. The crude product was purified by distillation at 0.8 mBar, collecting fractions that distilled at 80° C. to afford the desired material as a colourless liquid (2.70 g, 18.02%); 1H NMR (400.132 MHz, CDCl3) δ 1.93-1.70 (4H, m), 3.32-3.26 (1H, m), 3.60-3.47 (2H, m), 3.74-3.67 (1H, m), 4.50 (1H, septet), 6.28 (1H, t), 8.03 (1H, s).

Provenance & Evidence