反应详情

温度

-18 °C

To an oven dried 250 ml flask was charged with CH3MgBr (16.7 ml, 50 mmol, 3 M in Et2O) at r.t. under N2. It was then cooled down to −18° C. in a NaCl/ice bath, and 7-cyano-4-fluoroindole (2.0 g, 12.5 mmol) in dry THF (100 ml) was added dropwise using an addition funnel over 45 min. After 10 min, the reaction mixture was allowed to warm to r.t., and stirred for 2 hr. The reaction was slowly quenched with 5% sulfuric acid and the mixture stirred for 10 min. The reaction mixture was concentrated in vacuo and the residue poured into CHCl3 (150 ml). After neutralization with aqueous NH3 (50 ml), water (100 ml) was added, and the two layers were separated using a separation funnel. The aqueous layer was back extracted with CHCl3 (2×100 ml), and the combined organic extracts washed with H2O (100 ml), brine (100 ml), and dried (MgSO4). After evaporation in vacuo, the resulted crude compound was purified by flash chromatography (20% EtOAc/Hexane) to give 7-acetyl-4-fluoroindole (1.3 g, 59%) as a light gray solid. 1H NMR: (CDCl3) δ 10.55 (b s, 1H), 7.76 (dd, J=4.8, 8.3, 1H), 7.31 (app t, J=2.7, 1H), 6.83 (dd, J=8.4, 9.6, 1H), 6.67 (app t, J=2.9, 1H), 2.68 (s, 3H); HPLC Rt=1.343.

1. customTo an oven dried 250 ml flask
2. customover 45 min
3. temperatureto warm to r.t.
4. customThe reaction was slowly quenched with 5% sulfuric acid
5. stirringthe mixture stirred for 10 min
6. concentrationThe reaction mixture was concentrated in vacuo
7. additionthe residue poured into CHCl3 (150 ml)
8. additionAfter neutralization with aqueous NH3 (50 ml), water (100 ml) was added
9. customthe two layers were separated
10. extractionThe aqueous layer was back extracted with CHCl3 (2×100 ml)
11. washthe combined organic extracts washed with H2O (100 ml), brine (100 ml)
12. dry with materialdried (MgSO4)
13. customAfter evaporation in vacuo
14. customthe resulted crude compound
15. customwas purified by flash chromatography (20% EtOAc/Hexane)