1,2-Dichloroethane → 4'-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

Participants

Reaction Conditions

Reaction Steps

4′-(5-Aminomethyl-2-ethoxy-4-ethylimidazol-1-ylmethyl)-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (5.0 g, 11.0 mmol), (S)-2-acetylsulfanyl-4-methylpentanoic acid (dicyclohexylamine salt; 2.1 g, 11.0 mmol), 4-methylmorpholine (1.2 mL, 11.0 mmol), and 1-hydroxy-7-azabenzotriazole (1.5 g, 11.0 mmol) were combined and dissolved in DMF (120 mL, 1.6 mol) and then cooled at 0° C. for 10 minutes. EDC (2 mL, 11.0 mmol) was added and the mixture was stirred at 0° C. for 1 hour and then at room temperature for 2 hours. The reaction was quenched with water (100 mL), the product extracted with EtOAc (100 mL), and then concentrated. The mixture was purified by column chromatography (0-50% EtOAc:hexanes) to obtain the acetylsulfanyl ester intermediate, 4′-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester.

Provenance & Evidence