Lithium hydroxide, monohydrate → (2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acid

HRID 2425782Notes

Reaction equation

HRID 2425782 reaction equation
[C:1]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:14]([CH3:17])([CH3:16])[CH3:15])[C@H:9]([C:27]([O:29]C)=[O:28])[CH2:8]2)=[CH:3][CH:2]=1.O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[C:14]([CH3:15])([CH3:16])[CH3:17])[C@H:9]([C:27]([OH:29])=[O:28])[CH2:8]2)=[CH:3][CH:2]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57998017(2S,4R)-methyl 4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylate

Product 1

HCID 57998016(2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acidYield 83%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,4R)-methyl 4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylate (430 mg, 0.738 mmol) in THF (4 mL) and MeOH (4.00 mL) was added pre-made solution of lithium hydroxide monohydrate (61.9 mg, 1.476 mmol) in water (4 mL). The formed cloudy solution was stirred at room temperature for 5 h. Quenched with 5% citric acid, extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, evaporated, to afford the desired product (2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(butylthio)pyrrolidine-2-carboxylic acid (409 mg, 0.611 mmol, 83% yield) as a white foam. LC-MS (retention time: 3.49 min, method B), MS m/z 569 (M+H).

Workup

  1. customQuenched with 5% citric acid
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-6592fae3a9304e65a824587e2a20511a
Source dataset
uspto-grants-2011_06
Patent number
US07964560B2

Reaction notes

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