Imidazole → HCID 22876419, compound

HRID 2394126Notes

Reaction equation

HRID 2394126 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:10]([OH:26])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]2[O:23][CH2:24][O:25][C:19]=2[CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.[C:39]([Si:43]([CH3:46])([CH3:45])Cl)([CH3:42])([CH3:41])[CH3:40].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CO.C1COCC1.O>[C:1]([NH:8][C@@H:9]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:10]([O:26][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:22]=[CH:21][C:20]2[O:23][CH2:24][O:25][C:19]=2[CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 22876405HCID 22876405, compound

Product 1

HCID 22876419HCID 22876419, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 271 mg of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(3,4-methylenedioxyphenyl)methyl]hexanoic acid in 2.13 ml of DMF is treated, while being stirred, with 338 mg of imidazole and 415 mg of tert-butyldimethylchlorosilane. After having been stirred at RT for 20 h, the reaction solution is poured onto ice-water, and this mixture is extracted with ethyl acetate. The organic phase is washed with 10% citric acid solution and saline. A crude product is obtained which is dissolved in 7.13 ml of methanol and 2.75 ml of THF, with this solution then being treated, at RT, with a solution of 485 mg of potassium carbonate in 2.75 ml of water. The reaction mixture is stirred at RT for 2 h, concentrated down to approximately half its volume and poured onto 10% citric acid solution and ice; this mixture is then extracted with ethyl acetate. The organic phase is washed with (cold) saline. After drying over sodium sulfate, the solvent is evaporated and the residue is chromatographed on silica gel (eluent C), and the title compound is obtained. TLC Rf (C)=0.27. FAB-MS (M+H)+ =572.

Workup

  1. additionthe reaction solution is poured onto ice-water
  2. extractionthis mixture is extracted with ethyl acetate
  3. washThe organic phase is washed with 10% citric acid solution and saline
  4. customA crude product is obtained which
  5. stirringThe reaction mixture is stirred at RT for 2 h
  6. concentrationconcentrated down to approximately half its volume
  7. additionpoured onto 10% citric acid solution and ice
  8. extractionthis mixture is then extracted with ethyl acetate
  9. washThe organic phase is washed with (cold) saline
  10. dry with materialAfter drying over sodium sulfate
  11. customthe solvent is evaporated
  12. customthe residue is chromatographed on silica gel (eluent C)

Sources & evidence

ORD record
ord-f906415e487e47dd99a38204ad1609fa
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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