Hydrochloric Acid → 5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid

Participants

Reaction Steps

To a solution Ethyl 5-cyano-1H-indole-2-carboxylate (37 mg, 0.173 mmol), 2-[4-(trifluoromethoxy) phenoxy]ethanol (42 mg, 0.19 mmol) and Triphenylphosphine (227 mg, 0.518 mmol) in toluene (1 mL) was add DIAD (0.044 ml, 0.225 mmol) dropwise at RT. The reaction was let to stir overnight. The mixture was diluted with EtOAc and quenched with water. The two layers were separated, and the aqueous phase was further extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by normal phase silica chromatography. The eluting solvent was 0-30% EtOAc in Hexanes. The isolated ethyl 5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylate (15 mg, 0.04 mmol) was dissolved in THF (1 mL), MeOH (300 uL) and 1M NaOH (200 uL). The reaction went to completion in 5 hr. Water was added, the pH was adjusted to 3 with 1N HCl, and the solvent was removed in vacuo. EtOAc was added to the resulting aqueous solution. The two layers were separated, and the aqueous phase was further extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to yield 13.4 mg of the title product. HRMS: Calc for C19H13F3N2O4 413.0720. Found 413.0718

Provenance & Evidence