Methanol → 7-Fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indole-3-carboxylic acid

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Reaction Conditions

Reaction Steps

A mixture of 7 (23.4 g, 62.6 mmol) in MeOH (100 mL) and 5 M NaOH (100 mL) is heated at 80° C. overnight. LC/MS indicates that the reaction is complete. The reaction mixture is cooled to rt, and then concentrated in vacuo to remove most of the MeOH. The residue is dissolved in H2O, and then washed with Et2O once. The aqueous layer is slowly acidified to pH ˜2 with conc. HCl. The acidified suspension is extracted with Et2O, and the organic extract is washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is suspended in DCM/heptane (10/90). The white powder 8 (19.4 g, 96%) in the suspension is collected by suction filtration and air-dried. 1H NMR (CDCl3) δ 8.02 (s, 1H), 7.15-7.05 (m, 1H), 7.00-6.90 (m, 1H), 4.49 (t, J=5.0 Hz, 2H), 3.75 (t, J=4.9 Hz, 2H), 3.33 (s, 3H); 19F NMR (CDCl3) δ −57.74 (s, 3F), −135.65 (d, J=11.3 Hz, 1F); MS 363 (M+CH3CN+1), 322 (M+1, 100%).

Provenance & Evidence