Imidazole → HCID 22876415, compound

HRID 1377206Notes

Reaction equation

HRID 1377206 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:33][CH:32]=1)[C@@H:10]([OH:29])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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:45]([Si:49]([CH3:52])([CH3:51])Cl)([CH3:48])([CH3:47])[CH3:46].N1C=CN=C1>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:30][C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:35][CH:36]=1)[C@@H:10]([O:29][Si:49]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:52])[CH3:51])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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 22876401HCID 22876401, compound

Product 1

HCID 22876415HCID 22876415, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.19 g (5.4 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-(p-benzyloxyphenyl)-2(R)-[(4-biphenylyl)methyl]hexanoic acid in 55 ml of DMF are silylated, at RT for 20 h and under a protective gas, with 3.71 g (24.6 mmol) of tert-butyldimethylchlorosilane and 3.0 g (44 mmol) of imidazole. The reaction mixture is evaporated and the residue is taken up in ethyl acetate; this solution is then 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 64 ml of methanol and 15 ml of THF, and this solution is treated with 4.5 g of potassium carbonate and 15 ml of water and stirred at RT for 1 h. Working up in analogy with Example 88c), and medium pressure chromatography (gradient: 0-10% methanol in methylene chloride), results in the title compound: TLC Rf (B)=0.7; tRet (II)=22.7 min.

Workup

  1. customThe reaction mixture is evaporated
  2. washthis solution is then washed with sat. NaHCO3 solution, water and saline
  3. extractionThe aqueous phases are extracted 2× with ethyl acetate
  4. dry with materialthe organic phases are dried with Na2SO4
  5. customevaporated
  6. dissolutionThe residue is dissolved in 64 ml of methanol
  7. addition15 ml of THF, and this solution is treated with 4.5 g of potassium carbonate and 15 ml of water

Sources & evidence

ORD record
ord-a06688f881be46dab39fb8a0d0c73f77
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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