2-Amino-5-methylpyridine → (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M in toluene) (4.97 mL, 9.94 mmol) was added carefully to 5-methylpyridin-2-amine (1.075 g, 9.94 mmol) in toluene (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 15 minutes. (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (Intermediate AB3) (2 g, 4.97 mmol) in toluene (4 mL) was added. The reaction was heated to 120° C. for 1 hour in the microwave reactor and cooled to RT. The reaction mixture was concentrated. The residue was neutralised with citric acid (1M, aq) and then diluted with water and extracted with EtOAc. The combined organics were dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane to afford the product (1.800 g, 76%). 1H NMR (400 MHz, CDCl3) δ 1.04 (9H, s), 2.29 (3H, s), 3.65 (2H, t), 3.76-3.90 (5H, m), 4.31-4.37 (1H, m), 7.34-7.45 (6H, m), 7.48-7.54 (1H, m), 7.64-7.71 (4H, m), 8.07-8.13 (2H, m), 9.13 (1H, s); m/z (ES+) (M+H)+=479.60; HPLC tR=3.16 min.

Provenance & Evidence