Sodium Hydroxide → HCID 86698711, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 6-chloro-5-[4-(3-hydroxyoxetan-3-yl)-3-methoxyphenyl]-1H-indole-3-carboxylate (100 mg, 0.258 mmol) in methanol (3 mL) and sodium hydroxide (1M, 1.0 mL, 1.0 mmol) was heated to 70° C. for 24 hours. The reaction was concentrated under reduced pressure and the reaction was acidified with 1M hydrochloric acid aqueous to pH=2 then diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate two additional times. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure yielding 83 mg of the crude desired product. A portion of the crude material (60 mg) was purified by prep-HPLC (Phenomenex HILIC (Diol) 250×21.2 mm 5 μm; Mobile phase A: heptane; Mobile Phase B: Ethanol, gradient 95% A/5% B hold for 1.5 minutes, linear gradient to 0% A/100% B in 8.5 minutes, Hold at 0% A/100% B for 1 minutes; flow rate: 28 ml/min) to afford the title compound (16.9 mg, 17.5%) as a solid. MS (ES−) 372.0 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ 12.13 (br. s, 1H), 11.96 (br. s, 1H), 8.10 (d, J=2.2 Hz, 1H), 7.98 (s, 1H), 7.65 (s, 1H), 7.29 (d, J=7.8 Hz, 1H), 7.05 (d, J=1.5 Hz, 1H), 6.99 (dd, J=7.6, 1.5 Hz, 1H), 5.89 (s, 1H), 5.02 (d, J=6.8 Hz, 2H), 4.67 (d, J=6.8 Hz, 2H), 3.81 (s, 3H)

Provenance & Evidence