2-Amino-5-cyanopyridine → (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-cyanopyridin-2-yl)-2-hydroxypropanamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M in toluene) (0.621 mL, 1.24 mmol) was added to a solution of 6-aminonicotinonitrile (148 mg, 1.24 mmol) in toluene (10 mL) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 20 mins and then (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (Intermediate AB3) (250 mg, 0.62 mmol) was added. The reaction mixture was allowed to warm to room temperature and then heated at reflux under nitrogen for 4 hours. The reaction mixture was allowed to cool to room temperature and the concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water and DCM (50 mL). The organic layer was separated and the aqueous layer re-extracted with DCM (30 mL). The combined organics were dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane to afford the product (202 mg, 66.4%). 1H NMR (400 MHz, CDCl3) 1.04 (9H, s), 3.65-3.67 (2H, m), 3.81-3.91 (4H, m), 4.36 (1H, t), 7.35-7.45 (6H, m), 7.65-7.67 (4H, m), 7.92-7.95 (1H, m), 8.36-8.39 (1H, m), 8.54-8.56 (1H m), 9.43 (1H, s); m/z (ES+) (M+H)+=490; HPLC tR=3.08 min.

Provenance & Evidence