Hydrochloric Acid → 2-(4-(benzyloxy)-7-bromo-5-fluoro-1-methyl-1H-indol-3-yl)acetic acid

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Reaction Steps

To the solution of 33-3 (8 g, 24 mmol) in THF (30 mL) was added oxalyl chloride (15.4 g, 120 mmol) dropwised at 0° C. The mixture was stirred at room temperature overnight. The volatiles were evaporated to get a yellow residue, which was dissolved in 2,2′-oxydiethanol (50 mL). To the resulting solution were added hydrazine hydrate (6 mL) and potassium hydroxide (6.72 g, 120 mmol). The mixture was heated at 190° C. for 2 h before it was cooled to room temperature. Water (100 mL) was added to the mixture and neutralized with hydrochloric acid to pH=5, then extracted with ethyl acetate (2×50 mL). The organic layers were combined, washed with brine (4×50 mL), dried over MgSO4, filtered, and concentrated under vacuum. The resulting residue was purified on silica gel column chromatography eluting with dichloromethane/methanol (10:1) to afford 33-4 (5 g, 58%) as a yellow solid. LRMS: calc 391.0 and found: 392.1 [M+1].

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