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

HRID 2394083Notes

Reaction equation

HRID 2394083 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:35][CH:34]=1)[C@@H:10]([OH:31])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:47]([Si:51]([CH3:54])([CH3:53])Cl)([CH3:50])([CH3:49])[CH3:48].N1C=CN=C1>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:32][C:33]1[CH:34]=[CH:35][C:36]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:37][CH:38]=1)[C@@H:10]([O:31][Si:51]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:54])[CH3:53])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[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 228742795(S)-(Boc-Amino)-4(S)-hydroxy-6-(p-benzyloxyphenyl)-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

Product 1

HCID 156595645(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-(p-benzyloxy-phenyl)-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.44 g (3.90 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-(p-benzyloxyphenyl)-2(R)-[(p-benzyloxyphenyl)methyl]-hexanoic acid in 14 ml of DMF are stirred, under an N2 atmosphere, together with 2.70 g (17.6 mmol) of tert-butyldimethylchlorosilane and 2.18 g (32 mmol) of imidazole at RT for 18 h. The reaction mixture is poured onto ice-water, and this mixture is extracted with 3 portions of ethyl acetate; the organic phases are washed with 10% citric acid solution, H2O and saline, dried with Na2 SO4 and evaporated. The resulting oil is taken up in 30 ml of methanol/THF/H2O 3:1:1, and this solution is treated with 3.2 g of K2CO3 and stirred at RT for 1 h. The reaction mixture is partially evaporated, and the aqueous residue is poured onto 10% citric acid solution and ice, and this mixture is extracted 3× with ethyl acetate; the organic phases are washed twice with H2O and, finally, with saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate 2:1→1:1) of the crude product affords the title compound: TLC Rf (C)=0.53; FAB-MS (M+H)+ =740.

Workup

  1. additionThe reaction mixture is poured onto ice-water
  2. extractionthis mixture is extracted with 3 portions of ethyl acetate
  3. washthe organic phases are washed with 10% citric acid solution, H2O and saline
  4. customdried with Na2 SO4
  5. customevaporated
  6. additionthis solution is treated with 3.2 g of K2CO3
  7. customThe reaction mixture is partially evaporated
  8. additionthe aqueous residue is poured onto 10% citric acid solution and ice
  9. extractionthis mixture is extracted 3× with ethyl acetate
  10. washthe organic phases are washed twice with H2O
  11. dry with materialfinally, with saline, dried with Na2SO4
  12. customevaporated

Sources & evidence

ORD record
ord-85f8b960f98a40a5b0709882eba722a1
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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