Citric Acid → (2S,3R)-3-([(1S)-2,2-Dimethyl-1-([(1R)-1-phenylethyl]aminocarbonyl)propyl]aminocarbonyl)-2ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoic acid

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Reaction Steps

Lithium hydroxide hydrate (116 mg, 2.83 mmol) was added to a solution of methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoate (368 mg, 0.566 mmol) in methanol:water=10:1 (5 mL) and the mixture was stirred at room temperature for 2 h. The solution was neutralised with 5% aqueous citric acid and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (100 mL) and 5% aqueous citric acid (20 mL), washed with saturated aqueous sodium chloride (20 mL), dried MgSO4), and concentrated under reduced pressure. Purification by flash chromatography (eluting with dichloromethane:methanol=20:1 to 10:1) gave the title compound (62 mg, 18%) as a colourless glass, and some mixed fractions. These were combined and repurified by flash chromatography (eluting with ethyl acetate:hexane:acetic acid=33:66:1 to 50:50:1) to give the title compound (37 mg, 11%), as a white solid.

Provenance & Evidence