Sodium Carbonate → 4-Hydroxypiperidine-1-carbonitrile

Participants

Reaction Steps

To sodium bicarbonate (8.31 g, 99 mmol) was gradually added water (5 mL) with vigorous stirring to a uniform slurry. The flask was placed in an ice bath, and a solution of piperidin-4-ol (5 g, 49.4 mmol) in CH2Cl2 (12.5 mL) was added and the contents were vigorously mixed while cooling. To the above mixture was added a solution of cyanic bromide (6.28 g, 59.3 mmol) in CH2Cl2 (5 mL) dropwise over 15 min. After completion, the mixture was stirred for at 0° C. for 1 h, then at rt overnight. To the reaction mixture was added sodium carbonate (1.048 g, 9.89 mmol) to ensure complete neutralization. MgSO4 was added and the mixture was stirred vigorously for 15 min. The resulting suspension was filtered, rinsed with CH2Cl2. The filtrated was concentrated to afford 4-hydroxypiperidine-1-carbonitrile (5.11 g, 40.5 mmol, 82% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.61-1.73 (m, 3H) 1.95 (dddd, J=13.07, 7.01, 3.41, 3.28 Hz, 2H) 3.04-3.15 (m, 2H) 3.42-3.51 (m, 2H) 3.89 (tq, 1H).

Provenance & Evidence