Triethylamine → Rac-(cis)-2-[3-(2',4'-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid

Participants

Reaction Steps

[3-(2′,4′-Difluoro-biphenyl-4-yloxymethyl)-phenyl]-carbamic acid tert-butyl ester (111 mg, 0.269 mmol) was stirred in 5 mL EtOAc (saturated with HCl) at RT for 45 min. The mixture was evaporated, re-evaporated from EtOAc and pumped under high vacuum to give a solid. The crude product was dissolved in DMF (2 mL). To this solution, chilled in an ice bath, was added triethylamine (150 uL, 1.08 mmol), (cis)-cyclopentane-1,2-dicarboxylic acid (64 mg, 0.404 mmol) and HATU (154, 0.404 mmol) was added and then let stir at RT for 30 min. The reaction mixture was diluted with EtOAc (25 mL), washed with 1N HCl (10 mL), H2O (10 mL), saturated NaCl (10 mL), dried over MgSO4, filtered and evaporated to give a white solid. The crude product was purified by flash chromatography with a 0-55% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in hexanes to yield 64.8 mg of rac-(cis)-2-[3-(2′,4′-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid as a white solid.

Provenance & Evidence