Tributylphosphine → (1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

2-[3-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propan-1-ol (150 mg, 0.5276 mmol) is dissolved into anhydrous toluene (2 mL) and cooled in an ice bath to 0° C. with stirring under nitrogen. Tributyl phosphine (200 uL, 0.7914 mmol) is added by syringe followed by 1-1′-azodicarbonyl-dipiperidine (200 mg, 0.7914 mmol). Finally, (6-Hydroxy-1-methyl-1H-indol-3-yl)-acetic acid methyl ester (145 mg, 0.6596 mmol) is then added. The reaction is allowed to stir under nitrogen at 0° C. for 1 hour, then room temperature and monitored by TLC and HPLC. Upon completion, the reaction is diluted with hexanes and allowed to stir vigorously for 10 min. The resulting white precipitate is then filtered away and the solution is concentrated under vacuum. The residue is further purified using either EtOAc/Hexanes (1:9) or Acetone/Hexanes (1:9) gradients on silica gel chromatography to yield (1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl ester (150 mg, 0.309 mmol) or 59%.

Provenance & Evidence