Sodium Hydroxide → 6-Chloro-5-[4-(tetrahydro-2H-pyran-4-yl)phenyl]-1H-indole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 6-chloro-5-[4-(tetrahydro-2H-pyran-4-yl)phenyl]-1H-indole-3-carboxylate (360 mg, 0.973 mmol) in methanol (10 mL) was added sodium hydroxide (1 M, 4.0 mL, 4 mmol) and the reaction was heated to 70° C. for 24 hours. The reaction was concentrated under reduced pressure. The crude reaction was diluted with methanol (9 mL) to which was added additional sodium hydroxide (1M, 6.0 mL, 6 mmol) and heated to 70° C. for 24 hours. The reaction was concentrated under reduced pressure and acidified using 1N aqueous hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified using the Biotage Isolera One (SNAP 50 g silica gel column) and eluting with a gradient of 0-20% methanol/dichloromethane yielding 215 mg of the title compound as a solid. To a round bottom flask containing the title compound was added methanol (10 mL) and the reaction was heated to reflux. Additional methanol (5 mL) was added and the solution was allowed to cool to room temperature and stirred overnight at room temperature. The resulting precipitate was filtered and washed with 1 mL of methanol and dried by pulling high vacuum yielding 119 mg of the title compound. MS (ES−) 354.0 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.10 (s, 1 H), 11.93 (br. d, 1 H), 8.07 (d, 1 H), 7.93 (s, 1 H), 7.62 (s, 1 H), 7.21-7.46 (m, 4 H), 3.86-4.02 (m, 2H), 3.46 (td, 2 H), 2.71-2.93 (m, 1 H), 1.60-1.85 (m, 4 H).

Provenance & Evidence