Sodium Hydroxide → 4-Fluoro-2,3-dihydro-1H-indole

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-fluoro-1H-indole (950 mg, 7.03 mmol) in Acetic Acid (20 mL) at 12° C. under nitrogen was added sodium cyanoborohydride (1458 mg, 23.20 mmol) portionwise. The reaction was stirred at 12° C. for 2 hours, and at room temperature overnight. The reaction was worked up by pouring into sodium hydroxide (10 N). The aqueous was extracted with diethyl ether (3×100 mL), and the combined organics dried over sodium sulfate. LCMS analysis at this point indicated presence of product and some acylated product, along with some acylated starting material. The crude was dissolved in THF (10 mL) and treated with NaOH (6 N, 2 mL), then stirred at r.t. for 2 h. The reaction was stirred overnight, but no change in LCMS was observed, so the organic layer was removed, and the aqueous extracted with diethyl ether (2×10 mL), the combined organics were dried over sodium sulfate. The dried solution was filtered and concentrated, and the residue was purified by flash chromatography (0-25% EtOAc in hexanes, 24-g silica gel column) to afford 4-fluoro-2,3-dihydro-1H-indole (510 mg, 3.72 mmol, 52.9% yield) as a colorless oil. LC-MS (ES) m/z=138 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 2.94 (t, J=8.59 Hz, 2H), 3.48 (t, J=8.59 Hz, 2H), 5.79 (br. s., 1H), 6.23-6.35 (m, 2H), 6.87-6.99 (m, 1H).

Provenance & Evidence