2-Aminopyridine → (S)-2-hydroxy-N-(pyridin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M in toluene) (2.99 ml, 5.98 mmol) was added to pyridin-2-amine (0.563 g, 5.98 mmol) in toluene (20.18 ml) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (S)-methyl 2-hydroxy-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanoate (1 g, 2.99 mmol) (Intermediate AN1) in toluene (6.73 mL) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 5 hours. The reaction mixture was allowed to cool and concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water (25 mL) and extracted with EtOAc (2×50 mL). The combined organics were washed with brine (20 ml), then dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (0.657 g, 55.4%). 1H NMR (400 MHz, CDCl3) δ 1.03-1.17 (24H, m), 3.61-3.69 (3H, m), 3.82-3.86 (1H, m), 4.00-4.04 (1H, m), 4.13 (1H, d), 4.32 (1H, q), 7.02-7.06 (1H, m), 7.67-7.72 (1H, m), 8.23 (1H, d), 8.29-8.31 (1H, m), 9.20 (1H, s); m/z (ES+) (M+H)+=397.44; HPLC tR=3.36 min.

Provenance & Evidence