反应详情

温度

0 °C

Trimethylaluminium (3.73 mL, 7.45 mmol) was added to pyridin-2-amine (0.701 g, 7.45 mmol) in toluene (6 ml) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (1.5 g, 3.73 mmol) (Intermediate AB3) in toluene (6 ml) was added and the reaction was allowed to warm to room temperature and then heated to 110 for 5 hours in a microwave. 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), filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (1.085 g, 62.7%). 1H NMR: (400 MHz, CDCl3) δ 1.05 (9H, t), 3.60-3.66 (2H, m), 3.67 (1H, d), 3.82-3.84 (2H d, m), 3.80-3.85 (2H, m), 4.33-4.35 (1H, m), 7.03-7.06 (1H, m), 7.35-7.68 (10H, m), 7.70 (1H, d), 8.22 (1H, d), 8.29-8.30 (1H, m),9.15 (1H, s); m/z (ES+) (M+H)+=465.42; HPLC tR=3.13 min.

1. temperatureto warm to room temperature
2. temperatureheated to 110 for 5 hours in a microwave
3. temperatureto cool
4. concentrationconcentrated in vacuo
5. additiondiluted with water (25 mL)
6. extractionextracted with EtOAc (2×50 mL)
7. washThe combined organics were washed with brine (20 ml)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customevaporated
11. customThe crude product was purified by flash silica chromatography
12. washeluting with 30 to 50% EtOAc in isohexane