Trimethylsilyl cyanide → HCID 59200425, compound

Participants

Reaction Steps

TMSCN (0.3 mL, 2.28 mmol) followed by ZnI2 (51 mg, 0.16 mmol) were sequentially added to neat 1-(4-methylpyridin-2-yl)butan-1-one (372 mg, 2.28 mmol) with stirring under Ar. Reaction stirred at rt for 4 hours. THF (6 mL) was added to cyanohydrin, then this was slowly added dropwise over 10 min via cannula to LAH (140 mg, 3.6 mmol) in THF (10 mL) with stirring under Ar. Reaction warmed as addition progressed. Once addition was ended, reaction heated to reflux for 1 hour, then cooled to rt then in ice. To the cool reaction with stirring was added Na2SO4.10H2O, the reaction stirred overnight and was allowed to warm to RT as the bath warmed. The reaction was filtered, the solid washed with EtOAc; the organic phase extracted with 10% HCl (2×). The aqueous extracts were combined and washed with Et2O. Aqueous phase was basified to pH ˜12 with 5M NaOH, saturated with NaCl, then extracted with Et2O (3×). The combined extracts were dried (MgSO4), filtered and concentrated to afford 330 mg of 1-amino-2-(4-methylpyridin-2-yl)pentan-2-ol as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.36 (d, J=5.05 Hz, 1H), 7.18 (s, 1H), 7.00 (d, J=5.81 Hz, 1H), 3.04 (d, J=12.88 Hz, 1H), 2.90 (d, J=12.88 Hz, 1H), 2.37 (s, 3H), 1.71 (m, 2H), 1.40 (m, 1H), 0.77-0.95 (m, 4H).

Provenance & Evidence