Hydrochloric Acid → 4-(2-(2-Carboxy-ethyl)-3-{6-[3'-fluoro-5-(piperazine-1-carbonyl)-biphenyl-3-yloxy]-hexyl}-phenoxy)-butyric Acid

Participants

Reaction Steps

5-{6-[2-(2-Ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-3′-fluoro-biphenyl-3-carboxylic acid (150 mg), piperazine-1-carboxylic acid tert-butyl ester (54 mg), PyBroP (130 mg), diisopropylethylamine (85 □l) and dichloromethane (3 mL) were combined together and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate and concentrated to dryness. The total amount of the product obtained from the previous step was dissolved in ethanol (2 mL) and 10 M NaOH solution was added (3 eq.). The resulting reaction mixture was stirred at room temperature for 5 h. Then it was neutralized with 3 N HCl and extracted into ethyl acetate. The organic extract was dried over anhydrous sodium sulfate, concentrated to dryness, redissolved in a mixture of TFA and dichloromethane (1:1, 2 mL) and stirred at room temperature for 3 h. The solvents were removed under reduced pressure and the title compound was purified on reverse-phase HPLC.

Provenance & Evidence