反应详情

温度

0 °C

A suspension of NaH (8.1 g, 204 mmol, 60% in mineral oil) in DMF (100 mL) at 0° C. is treated with 4-(5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (3 g, 13.6 mmol) and stirred at 0° C. for 0.5 h. The mixture is treated with HOSA (7.7 g, 68 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice, filtered through a pad of Celite, and extracted with EtOAc (3×100 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by filtration through a short plug of silica gel to afford 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol, which is used in the next step without further purification. MS: 237 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.30 (m, 1H), 7.22 (m, 1H), 6.98 (m, 2H), 4.71 (s, NH2, 2H), 2.75 (m, 2H), 1.86 (m, 2H), 1.31 (s, 6H).

1. additionThe mixture is treated with HOSA (7.7 g, 68 mmol) portion wise
2. temperaturewarmed to rt over 2 h
3. additionThe mixture is then poured over ice
4. filtrationfiltered through a pad of Celite
5. extractionextracted with EtOAc (3×100 mL)
6. dry with materialThe combined organic layer is dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. filtrationThe residue is purified by filtration through a short plug of silica gel