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

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (1.966 mL, 3.93 mmol) was added slowly to 5-methylpyridin-2-amine (0.407 g, 3.76 mmol) in toluene (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-((S)-2-(tert-butyldimethylsilyloxy)propoxy)-2-hydroxypropanoate (Intermediate AS3) (1 g, 3.42 mmol) in toluene (4 mL) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 4 hours (a further 5ml toluene was added to aid stirring). The reaction mixture was concentrated in vacuo. 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 to afford the product (0.994 g) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 0.07 (6H, d), 0.88 (9H, s), 1.15 (3H, d), 2.30 (3H, s), 2.79-3.11 (1H, m), 3.39-3.51 (2H, m), 3.80-3.91 (2H, m), 3.94-4.03 (1H, m), 4.31-4.36 (1H, m), 7.49-7.56 (1H, m), 8.09-8.16 (2H, m), 9.20 (1H, s); m/z (ES+) (M+H)+=369.52; HPLC tR=2.73 min.

Provenance & Evidence