Water → HCID 11317482, compound

HRID 1865757Notes

Reaction equation

HRID 1865757 reaction equation
[CH3:1][O:2][C@@H:3]([C:28]([CH3:36])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:29])[C:4]([NH:6][C@@H:7]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:8]([N:10]([CH3:23])[C@@H:11]([CH:20]([CH3:22])[CH3:21])/[CH:12]=[C:13](\[CH3:19])/[C:14]([O:16]CC)=[O:15])=[O:9])=[O:5].CO[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>[CH3:1][O:2][C@@H:3]([C:28]([CH3:36])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH3:29])[C:4]([NH:6][C@H:7]([C:8]([N:10]([CH3:23])[C@@H:11]([CH:20]([CH3:22])[CH3:21])/[CH:12]=[C:13](\[CH3:19])/[C:14]([OH:16])=[O:15])=[O:9])[C:24]([CH3:25])([CH3:26])[CH3:27])=[O:5]

Participants

7

Reactant 4

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86596613HCID 86596613, compoundHCID 86596614HCID 86596614, compound

Product 1

HCID 11317482HCID 11317482, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

According to General Procedure II, a 1:1 mixture of ethyl (E,4S)-4-[((2S)-2-{[(2S)-2-methoxy-3-methyl-3-phenylbutanoyl]amino}-3,3-dimethylbutanoyl)(methyl)amino]-2,5-dimethyl-2-hexenoate and ethyl (E,4S)-4-[((2S)-2-{[(2R)-2-methoxy-3-methyl-3-phenylbutanoyl]amino}-3,3-dimethylbutanoyl)(methyl)amino]-2,5-dimethyl-2-hexenoate (1.0 g, 2.0 mmol, from Reference Example 104) is dissolved in methanol (10 mL) and tetrahydrofuran (10 mL). To this solution is added water (5 mL) and lithium hydroxide monohydrate (0.17 g, 4.0 mmol), and the resulting mixture is stirred at 60° 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 (240 mg) is subjected to HPLC purification (Prodigy OS3 column, acetonitrile/water/TFA) to give (E,4S)-4-[{N-[(2S)-2-methoxy-3-methyl-3-phenylbutanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoic acid as a hard white foam (50 mg). MS (ES+): (M+H)=475.0

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 (240 mg) is subjected to HPLC purification (Prodigy OS3 column, acetonitrile/water/TFA)

Sources & evidence

ORD record
ord-4932906016a848c7b2c50e4201c31ae5
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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