Imidazole → HCID 22876422, compound

HRID 1585311Notes

Reaction equation

HRID 1585311 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]([CH2:23][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]([CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=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 22876408HCID 22876408, compound

Product 1

HCID 22876422HCID 22876422, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5.08 g (9.81 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-{[p-(2-phenylethyl)phenyl]methyl}hexanoic acid in 22 ml of DMF are silylated, under a protective gas, with 6.80 g (45.1 mmol) of tert-butyldimethylchlorosilane and 5.48 g (80.4 mmol) of imidazole at RT for 20 h. The reaction mixture is poured onto 500 ml of ice-water, and this mixture is extracted 3× with ethyl acetate. The organic phases are washed with 10% citric acid solution, 2× water and saline, dried with Na2SO4 and evaporated. The residue is dissolved in 119 ml of methanol and 46 ml of THF, and this solution is treated with 8.1 g of potassium carbonate and 46 ml of water, and then stirred at RT for 17 h. The reaction mixture is subsequently poured onto ice-cold 10% citric acid solution, and this mixture is 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→1:1→ethyl acetate) results in the pure title compound: TLC Rf (D)=0.22; tRet (II)=23.3 min.

Workup

  1. extractionthis mixture is extracted 3× with ethyl acetate
  2. washThe organic phases are washed with 10% citric acid solution, 2× water and saline
  3. dry with materialdried with Na2SO4
  4. customevaporated
  5. dissolutionThe residue is dissolved in 119 ml of methanol
  6. addition46 ml of THF, and this solution is treated with 8.1 g of potassium carbonate and 46 ml of water
  7. additionThe reaction mixture is subsequently poured onto ice-cold 10% citric acid solution
  8. extractionthis mixture is extracted 3× with ethyl acetate
  9. washThe organic phases are washed with 2 portions of water and saline
  10. dry with materialdried with Na2SO4
  11. customevaporated

Sources & evidence

ORD record
ord-26835706f8d74aa2b347cd75d6f96dd3
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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