Water → HCID 69021294, compound

Participants

Reaction Conditions

Reaction Steps

A 1:1 mixture of ethyl (E,4S)-4-[((2S)-2-{[(2S)-2-hydroxy-3-methyl-3-phenylbutanoyl]amino}-3,3-dimethylbutanoyl)(methyl)amino]-2,5-dimethyl-2-hexenoate and ethyl (E,4S)-4-[((2S)-2-{[(2R)-2-hydroxy-3-methyl-3-phenylbutanoyl]amino}-3,3-dimethylbutanoyl)(methyl)amino]-2,5-dimethyl-2-hexenoate (0.34 g, 0.70 mmol, from Reference Example 41) is dissolved in methanol (3.2 mL) and tetrahydrofuran (3.2 mL). To this solution is added water (1.6 mL) and lithium hydroxide monohydrate (64 mg, 1.5 mmol), and the resulting mixture is stirred at 65° C. for 16 hours. Solvents are removed in vacuo and the residue is then dissolved in water. The solution is acidified to pH 1 with 2 M aqueous hydrochloric acid solution and then extracted thrice with ethyl acetate. The combined extracts are washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure to afford a white foam. A sample of this crude material (200 mg) is subjected to HPLC purification (Prodigy OS3 column, acetonitrile/water/TFA) to give (E,4S)-4-[{N-[(2R)-2-hydroxy-3-methyl-3-phenylbutanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoic acid as a white foam, which is crushed to a powder (50 mg). MS (ES+): (M+H)=461.0

Provenance & Evidence