Hydrochloric Acid → 3-[[[[4'-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-(isopropylthio)-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate

Participants

Reaction Steps

To a solution of 4′-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-(isopropylthio)-4-biphenylcarboxylic acid (150 mg) in tetrahydrofuran (1.5 ml) was added N,N′-carbonyldiimidazole (64 mg) and stirred at room temperature for 30 minutes. To the mixture were added 3-(aminosulfonyl)propyl acetate (67 mg) and 1,8-diazabicyclo[5.4.0]-7-undecene (55 μl) and stirred at room temperature, and then stirred at 50° C. for 3 hours. The reaction mixture was poured into 0.1N hydrochloric acid and ethyl acetate and the organic layer was separated. The organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo to give 3-[[[[4′-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-3-(isopropylthio)-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate (72 mg). To a solution of the product (72 mg) in methanol (2.0 ml) and tetrahydrofuran (2.0 ml) was added sodium hydroxide aqueous solution (1N, 532 μl) and stirred at room temperature for 10 minutes. To the mixture was added hydrochloric acid aqueous solution (1N, 532 μl) and diluted with ethyl acetate. The solution was poured into water and ethyl acetate and the organic layer was separated. The organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified with silica gel column chromatography to give tert-butyl [(2R)-2-(3-chlorophenyl)-2-hydroxyethyl][2-[4′-[[[(3-hydroxypropyl)sulfonyl]amino]carbonyl]-3′-(isopropylthio)-4-biphenylyl]-ethyl]carbamate (49 mg).

Provenance & Evidence