反应详情

温度

0 °C

Trimethylaluminium (2M solution in toluene) (2.86 mL, 5.71 mmol) was added to 5-fluoropyridin-2-amine in toluene (8 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 (Intermediate AB3) in toluene (8 mL) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 24 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 (30 mL) and extracted with EtOAc (2×50 mL). The combined organics were 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 (1.32 g, 55%). 1H NMR (400 MHz, CDCl3) δ 1.05 (s, 9H), 3.60-3.68 (m, 3H), 3.79-3.83 (m, 2H), 3.86 (d, 2H), 4.31-4.35 (m, 1H), 7.34-7.46 (m, 7H), 7.64-7.69 (m, 4H), 8.14 (d, 1H), 8.22-8.28 (m, 1H), 9.18 (s, 1H); m/z (ES+), (M+H)+=483.63; HPLC tR=3.08 min.

1. temperatureto warm to room temperature
2. temperatureheated
3. temperatureat reflux for 24 hours
4. temperatureto cool
5. concentrationconcentrated in vacuo
6. additiondiluted with water (30 mL)
7. extractionextracted with EtOAc (2×50 mL)
8. dry with materialThe combined organics were dried (MgSO4)
9. customevaporated
10. customThe crude product was purified by flash silica chromatography
11. washeluting with 30 to 50% EtOAc in isohexane