4-Fluoroaniline → 1,2-Bis(4-fluorophenyl)-1H-indole-5-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Under an inert atmosphere of nitrogen, a mixture of methyl 4-chloro-3-(2-(4-fluorophenyl)ethynyl)benzoate (200 mg, 0.69 mmol, 1.00 equiv), 4-fluoroaniline (152.8 mg, 1.39 mmol, 2.00 equiv), X-Phos (65.2 mg, 0.14 mmol, 0.20 equiv), Pd2(dba)3 (63.8 mg, 0.07 mmol, 0.10 equiv), t-BuOK (388.8 mg, 3.47 mmol, 5.00 equiv), and toluene (8 mL) was stirred overnight at 100° C. in an oil bath. The resulting mixture was concentrated in vacuo, and purified via silica gel column chromatography (ethyl acetate/petroleum ether (1:1)). The crude product (160 mg) was purified by Prep-HPLC with the following conditions (AGILENT Pre-HPLC (MS-Directed)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (50% CH3CN up to 70% in 10 min); Detector, UV 254 nm. This resulted in 26 mg (11%) of 1,2-bis(4-fluorophenyl)-1H-indole-5-carboxylic acid as a white solid.

Provenance & Evidence