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

HRID 1585369Notes

Reaction equation

HRID 1585369 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][O:42][CH3:43])=[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:44]([Si:48]([CH3:51])([CH3:50])Cl)([CH3:47])([CH3:46])[CH3:45].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][CH2:41][O:42][CH3:43])=[CH:37][CH:38]=1)[C@@H:10]([O:31][Si:48]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:51])[CH3:50])[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]([CH3:6])([CH3:5])[CH3:7])=[O:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 228763995(S)-(Boc-Amino)-4(S)-hydroxy-6-[p-(2-methoxyethoxy)phenyl]-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

Product 1

HCID 228764135(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-[p-(2-methoxyethoxy)phenyl]-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.85 g (6.48 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-[p-(2-methoxyethoxy)-phenyl]-2(R)-[(p-benzyloxyphenyl)methyl]hexanoic acid in 11 ml of DMF are silylated, at RT for 16 h and under a protective gas, with 4.49 g (29.8 mmol) of tert-butyldimethylchlorosilane and 3.6 g (53.1 mmol) of imidazole. The reaction mixture is poured onto ice-water and the whole is extracted 3 times with ethyl acetate. The organic phases are washed with 10% citric acid solution, 2 times with water and with saline, dried with Na2SO4 and evaporated. The residue is dissolved in 79 ml of methanol and 30 ml of THF, and this solution is treated with 5.37 g of potassium carbonate and 30 ml of water and stirred at RT for 3 h. The reaction mixture is subsequently poured onto an ice-cold 10% citric acid solution, and this mixture is extracted 3 times with ethyl acetate. The organic phases are washed with 2 portions of H2O and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 1:1) affords the title compound: TLC Rf (C)=0.28; tRet (II)=20.9 min.

Workup

  1. additionThe reaction mixture is poured onto ice-water
  2. extractionthe whole is extracted 3 times with ethyl acetate
  3. washThe organic phases are washed with 10% citric acid solution, 2 times with water and with saline
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. dissolutionThe residue is dissolved in 79 ml of methanol
  7. addition30 ml of THF, and this solution is treated with 5.37 g of potassium carbonate and 30 ml of water
  8. additionThe reaction mixture is subsequently poured onto an ice-cold 10% citric acid solution
  9. extractionthis mixture is extracted 3 times with ethyl acetate
  10. washThe organic phases are washed with 2 portions of H2O and saline
  11. dry with materialdried with Na2SO4
  12. customevaporated

Sources & evidence

ORD record
ord-10441765c21e4465b9ed681c6b4a831b
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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