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

HRID 1585334Notes

Reaction equation

HRID 1585334 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[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:39]([Si:43]([CH3:46])([CH3:45])Cl)([CH3:42])([CH3:41])[CH3:40].N1C=CN=C1>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C@@H:10]([O:31][Si:43]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:46])[CH3:45])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:21][CH:22]=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 228742955(S)-(Boc-Amino)-4(S)-hydroxy-6-phenyl-2(R)-[(p-benzyloxyphenyl)methyl]-hexanoic acid

Product 1

HCID 156595625(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-phenyl-2(R)-[(p-benzyloxylphenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.4 g (2.69 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(p-benzyloxyphenyl)methyl]-hexanoic acid in 2.9 ml of DMF are stirred, at RT for 18 h, together with 1.87 g (12.4 mmol) of tert-butyldimethylchlorosilane and 1.5 g (22 mmol) of imidazole. The reaction mixture is then poured onto ice water, and this mixture is extracted with 3 portions of ethyl acetate; the combined organic phases are washed with 10% citric acid solution, water and saline, dried with sodium sulfate and evaporated. An oil is obtained. This is followed by hydrolysis of the silyl ester function of the oil, at RT, using 2.2 g of potassium carbonate in 63 ml of methanol/water/THF,3:1:1, and partial evaporation at RT. The aqueous residue is poured onto 10% citric acid solution and ice, and this mixture is extracted 3 times with ethyl acetate; the organic phases are washed twice with water and saline, dried with sodium sulfate and evaporated. Column chromatography (SiO2, D) of the crude product yields the title compound: TLC Rf (D)=0.17; tRet (I)=33.7 min; FAB-NS (M+H)+ =634.

Workup

  1. additionThe reaction mixture is then poured onto ice water
  2. extractionthis mixture is extracted with 3 portions of ethyl acetate
  3. washthe combined organic phases are washed with 10% citric acid solution, water and saline
  4. dry with materialdried with sodium sulfate
  5. customevaporated
  6. customAn oil is obtained
  7. custom2.2 g of potassium carbonate in 63 ml of methanol/water/THF,3:1:1, and partial evaporation at RT
  8. additionThe aqueous residue is poured onto 10% citric acid solution and ice
  9. extractionthis mixture is extracted 3 times with ethyl acetate
  10. washthe organic phases are washed twice with water and saline
  11. dry with materialdried with sodium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-607b12750ca94ffb858863d289cc3b02
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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