Sodium hydride → HCID 43438759, compound

Participants

Reaction Conditions

Reaction Steps

In an oven dried 20 mL scintillation vial, indole-3-carboxylic acid (500 mg, 3.10 mmol) was massed. The vial was charged with a stir bar and DMF (10 mL), and then capped under an atmosphere of nitrogen. The solution was cooled to 0° C., followed by addition of NaH (60% dispersion in mineral oil, 375 mg, 9.38 mmol). The reaction was allowed to stir for 5 min. 4-Bromo-2-fluorobenzyl bromide (1.00 g, 3.73 mmol) was added in one portion, and the reaction was allowed to stir 15 min at 0° C. then warmed to 25° C. over 30 min. Reaction was monitored by LCMS, and upon completion was quenched cautiously with H2O. The reaction mixture was diluted with dichloromethane (20 mL) and the organic layer was acidified to pH 1 with 1M HCl. The aqueous layer was extracted with dichloromethane (3×20 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with hexanes/ethyl acetate (0 to 100%) to afford 1-(4-bromo-2-fluorobenzyl)-1H-indole-3-carboxylic acid as a solid (LCMS: RT=0.795 min, (M+H)+ m/z=348).

Provenance & Evidence