Imidazole → 5(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-(p-benzyloxyphenyl)-2(R)-[(p-methoxyphenyl)methyl]hexanoic acid

HRID 1585317Notes

Reaction equation

HRID 1585317 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:29][CH:28]=1)[C@@H:10]([OH:25])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:41]([Si:45]([CH3:48])([CH3:47])Cl)([CH3:44])([CH3:43])[CH3:42].N1C=CN=C1>C(OCC)(=O)C>[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:31][CH:32]=1)[C@@H:10]([O:25][Si:45]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:48])[CH3:47])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 228764025(S)-(Boc-Amino)-4(S)-hydroxy-6-(p-benzyloxyphenyl)-2(R)-[(p-methoxyphenyl)-methyl]hexanoic acid

Product 1

HCID 228764165(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-(p-benzyloxyphenyl)-2(R)-[(p-methoxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2.5 g (4.54 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-(p-benzyloxy-phenyl)-2(R)-[(p-methoxyphenyl)methyl]hexanoic acid in 42 ml of DMP are silylated, under a protective gas, with 3.15 g (20.9 mmol) of tert-butyldimethylchlorosilane and 2.53 g (37.3 mmol) of imidazole at RT for 20 h. The reaction mixture is diluted with ethyl acetate, and this mixture is washed with sat. NaHCO3 solution, water and saline. The aqueous phases are extracted 2× with ethyl acetate, and the organic phases are dried with Na2SO4 and evaporated. The residue is dissolved in 50 ml of methanol and 13 ml of THF, and this solution is treated with 3.8 g of potassium carbonate and 13 ml of water, and stirred at RT for 1 h. Subsequently, the reaction mixture is partially evaporated and the residue is diluted with ice-cold 10% citric acid solution; this mixture is then extracted 3× with ethyl acetate. The organic phases are washed with 2 portions of water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 2:1) results in the pure title compound: TLC Rf (C)=0.13; tRet (II)=21.7 min. 7d) 5(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-(p-benzyloxyphenyl)-2(R)-[(p-methoxyphenyl)methyl]hexanoyl-(L)-Val-N-(2-methoxyethyl)amide

Workup

  1. washthis mixture is washed with sat. NaHCO3 solution, water and saline
  2. extractionThe aqueous phases are extracted 2× with ethyl acetate
  3. dry with materialthe organic phases are dried with Na2SO4
  4. customevaporated
  5. dissolutionThe residue is dissolved in 50 ml of methanol
  6. addition13 ml of THF, and this solution is treated with 3.8 g of potassium carbonate and 13 ml of water
  7. customSubsequently, the reaction mixture is partially evaporated
  8. additionthe residue is diluted with ice-cold 10% citric acid solution
  9. extractionthis mixture is then extracted 3× with ethyl acetate
  10. washThe organic phases are washed with 2 portions of water and saline
  11. dry with materialdried with Na2SO4
  12. customevaporated

Sources & evidence

ORD record
ord-2569f3538059457e8c0f0e4e9fb82b56
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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