Trimethylsilyl cyanide → HCID 59200374, compound

Participants

Reaction Steps

TMSCN (1.10 mL, 8.25 mmol) followed by ZnI2 (163 mg, 0.51 mmol) were sequentially added to neat 1-(pyridin-2-yl)butan-1-one (1.131 g, 7.58 mmol) with stirring under Ar. The reaction was stirred at RT for 1 hour. THF (13 mL) was added to cyanohydrin, then this was slowly added dropwise over 10 min via cannula to LAH (462 mg, 12.17 mmol) in THF (30 mL) with stirring under Ar. The reaction warmed as addition progressed. Once the addition ended, the reaction was heated to reflux for 1 hour, then cooled to RT then cooled in ice. To the cooled reaction mixture was added with stirring Na2SO4.10H2O. The reaction stirred overnight and was allowed to warm to RT as the bath warmed. The reaction was filtered, solid washed with EtOAc, the organic phase extracted with 10% HCl (2×), aqueous extracts combined and washed with Et20. The aqueous phase was basified to pH ˜12 with 5M NaOH, saturated with NaCl, and then extracted with Et2O (3×). Combined extracts were dried (MgSO4), filtered and concentrated to afford 695 mg of 1-amino-2-(pyridin-2-yl)pentan-2-ol as an oil. 1H NMR showed this to be a 1:1.6 mixture of ROTMS:ROH:1H NMR for desired product: 1H NMR (400 MHz, CDCl3) δ ppm 8.53 (m, 1H), 7.64 (td, J=7.58, 1.77 Hz, 1H), 7.58 (dt, J=7.83, 1.14 Hz, 1H), 7.10 (ddd, J=7.33, 4.80, 1.26 Hz, 1H), 3.32 (d, J=13.64 Hz, 1H), 2.87 (d, J=13.64 Hz, 1H), 0.75 (m, 3H)

Provenance & Evidence