Cyanogen Bromide → 4-[(1R)-1-hydroxyethyl]-1-piperidinecarbonitrile

Participants

Reaction Steps

(1R)-1-(4-Piperidinyl)ethanol acetic acid salt (Example 167, Step 1, 568 mg, 3 mmol, 94% ee) and sodium acetate (2.46 g, 30 mmol) in MeOH (30 mL) was stirred at room temperature for 15 min. A solution of cyanogen bromide (953 mg, 9 mmol) in CH2Cl2 (4 mL) was added at 0° C. The mixture was stirred from 0° C. to 25° C. for 12 h. The salt was removed by filtration and washed by CH2Cl2. After concentration, the crude product was purified by chromatography on a silica gel column using 70% EtOAc/CH2Cl2 to give 480 mg (99%) of 4-[(1R)-1-hydroxyethyl]-1-piperidinecarbonitrile as an oil. 1H NMR (400 MHz, CDCl3): δ 3.69 (s, 1H), 3.67-3.57 (m, 1H), 3.54-3.43 (m, 2H), 3.08-2.94 (m, 2H), 1.96-1.84 (m, 1H), 1.67-1.65 (m, 1H), 1.53-1.35 (m, 3H), 1.20 (d, 3H, J=6.3 Hz).

Provenance & Evidence