2-Methyl-2-butene → 6-chloro-5-{4-[1-(methylsulfonyl)pyrrolidin-2-yl]phenyl}-1H-indole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 6-chloro-5-{4-[1-(methylsulfonyl)pyrrolidin-2-yl]phenyl}-1H-indole-3-carbaldehyde (75 mg, 0.19 mmol) in acetonitrile/t-butanol (4.5 mL/4.5 mL) was added 2-methyl-2-butene (3.00 mL, 28.2 mmol). The reaction mixture was cooled to 0° C. followed by the addition of an aqueous solution of sodium chlorite (377 mg, 5.58 mmol) and sodium phosphate (monobasic and monohydrate, 770 mg, 5.58 mmol) in water (9 mL) dropwise via additional funnel. The ice bath was removed and the reaction was stirred at room temperature overnight. The following morning, 2-methyl-2-butene (1.50 mL, 14.1 mmol) and an aqueous solution of sodium chlorite (125 mg, 1.86 mmol) and sodium phosphate (monobasic and monohydrate, 257 mg, 1.86 mmol) in water (3 mL) was added in a dropwise manner. The reaction was allowed to stir overnight at room temperature. The reaction was quenched with sodium sulfite (940 mg, 7.44 mmol) in water (3 mL). The reaction mixture was concentrated under reduced pressure to remove the volatile organics. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to give the desired product (40.1 mg, 51.2% yield). MS (ES+) 441.0 (M+Na)+. 1H NMR (400 MHz, DMSO-d6) δ 11.95 (s, 1H), 8.07 (s, 1H), 7.95 (s, 1H), 7.64 (s, 1H), 7.40 (m, 4H), 4.94-4.91 (m, 1H), 3.51-3.49 (s, 2H), 2.95 (s, 3H), 2.40-2.30 (m, 1H), 1.91-1.86 (m, 3H).

Provenance & Evidence