Water → HCID 11282608, compound

HRID 1865760Notes

Reaction equation

HRID 1865760 reaction equation
[OH:1][C@@H:2]([C:27]([CH3:35])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH3:28])[C:3]([NH:5][C@@H:6]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:7]([N:9]([CH3:22])[C@@H:10]([CH:19]([CH3:21])[CH3:20])/[CH:11]=[C:12](\[CH3:18])/[C:13]([O:15]CC)=[O:14])=[O:8])=[O:4].O[C@H](C(C)(C1C=CC=CC=1)C)C(N[C@@H](C(C)(C)C)C(N(C)[C@@H](C(C)C)/C=C(\C)/C(OCC)=O)=O)=O.O.O.[OH-].[Li+]>CO.O1CCCC1>[OH:1][C@@H:2]([C:27]([CH3:35])([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH3:28])[C:3]([NH:5][C@H:6]([C:7]([N:9]([CH3:22])[C@@H:10]([CH:19]([CH3:21])[CH3:20])/[CH:11]=[C:12](\[CH3:18])/[C:13]([OH:15])=[O:14])=[O:8])[C:23]([CH3:24])([CH3:25])[CH3:26])=[O:4]

Participants

7

Reactant 4

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86596615HCID 86596615, compoundHCID 86596616HCID 86596616, compound

Product 1

HCID 11282608HCID 11282608, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

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-[(2S)-2-hydroxy-3-methyl-3-phenylbutanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoic acid as a hard white foam, which is crushed into a powder (50 mg). MS (ES+): (M+H)=461.0

Workup

  1. customSolvents are removed in vacuo
  2. dissolutionthe residue is then dissolved in water
  3. extractionextracted thrice with ethyl acetate
  4. washThe combined extracts are washed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customdecanted
  7. concentrationconcentrated under reduced pressure
  8. customto afford a white foam
  9. customA sample of this crude material (200 mg) is subjected to HPLC purification (Prodigy OS3 column, acetonitrile/water/TFA)

Sources & evidence

ORD record
ord-de951bc6aae9424ab5d1b6398eaa33f5
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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