Sodium Carbonate → 4-Hydroxypiperidine-1-carbonitrile

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).

1. customThe flask was placed in an ice bath
2. additionthe contents were vigorously mixed
3. temperaturewhile cooling
4. stirringAfter completion, the mixture was stirred for at 0° C. for 1 h
5. customat rt
6. customovernight
7. stirringthe mixture was stirred vigorously for 15 min
8. filtrationThe resulting suspension was filtered
9. washrinsed with CH2Cl2
10. concentrationThe filtrated was concentrated

ORD record

ord-eedf3a7185b44d5d8482f59eb5fcb045

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940716B2