1H-Indole, 7-fluoro-4-(trifluoroMethyl)- synthesis

Yield:1167055-51-7 19%

Reaction Conditions:

Stage #1: 1-fluoro-2-nitro-4-trifluoromethyl-benzene;vinyl magnesium bromide in tetrahydrofuran at -78; for 1 h;
Stage #2: with ammonium chloride in tetrahydrofuran;

Steps:

13.A

A. 7-Fluoro-4-trifluoromethyl-1 /-/-indole To a mixture of 1-fluoro-2-nitro-4-trifluoromethyl-benzene (3.27 ml_, 23.3 mmol) in THF (100 ml_) at -78 ⁰C is added vinylmagnesium bromide (100 ml_, 0.7 M in THF, 70 mmol) slowly over a 30 min period. After this mixture is stirred at -78 °C for 30 min, sat. NH₄CI is added, and the cooling bath is removed. The reaction mixture is partitioned between H₂O and EtOAc, and the two layers are separated. The organic layer is washed with H₂O and brine, dried over MgSO₄, filtered, and concentrated in vacuo. The crude material is purified on silica gel with heptane/EtOAc (100/0 to 50/50) as eluant to give 0.93 g (19%) of the product as a brown oil. ¹H NMR (CDCI₃): δ 8.53 (br, s, 1 H), 7.50-7.15 (m, 2 H), 7.00-6.85 (m, 1 H), 6.85-6.70 (m, 1 H); ¹⁹ F NMR (CDCI₃): δ -60.56 (s, 3F), -129.63 (d, J = 11.3 Hz, 1 F); MS 203 (M+, 100%).

References:

WO2011/22449,2011,A1 Location in patent:Page/Page column 78-79