Potassium Sodium Tartrate → (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-fluoropyridin-2-yl)-2-hydroxypropanamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M solution in toluene) (15.89 mL, 31.79 mmol) was added to 5-fluoropyridin-2-amine (3.10 g, 27.64 mmol) in toluene (80 mL) cooled to 0° C. under nitrogen over a period of 10 minutes. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (8 g, 27.64 mmol) in toluene (20 mL) was added over 10 minutes and the reaction was allowed to warm to room temperature and then heated at 90° C. for 2 hours. The reaction mixture was cooled and poured into a 20% solution of Rochelle's salt (50 mL), diluted with ethyl acetate (200 mL) and stirred for 2 hours. The organic phase was separated, washed with water and brine, dried (MgSO4) filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane to afford the product (5.28 g, 51.7%). 1H NMR (400 MHz, CDCl3) δ 0.028 (3H, s), 0.033 (3H, s), 0.87 (9H, s), 2.90 (2H, d), 3.02-3.08 (2H, m), 3.68-3.74 (2H, m), 4.00 (1H, t), 4.41-4.48 (1H, m), 7.41-7.45 (1H, m), 8.15 (1H, d), 8.21-8.24 (1H, m), 9.85 (1H, s); m/z (ES+) (M+H)+=370; HPLC tR=1.97 min.

Provenance & Evidence