Imidazole → HCID 22874310, compound

HRID 2394149Notes

Reaction equation

HRID 2394149 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([OH:25])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[O:23][CH3:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.[C:38]([Si:42]([CH3:45])([CH3:44])Cl)([CH3:41])([CH3:40])[CH3:39]>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([O:25][Si:42]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:45])[CH3:44])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[O:23][CH3:24])[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 22874287HCID 22874287, compound

Product 1

HCID 22874310HCID 22874310, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 500 mg of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2-methoxyphenyl)methyl]hexanoic acid in 5 ml of DMF is treated, while being stirred, with 614 mg of imidazole and 796 mg of tert-butyldimethylchlorosilane. After it has been stirred at RT for 20 h, the reaction solution is poured onto ice-water and the whole is extracted with ethyl acetate. The organic phase is washed with 10% citric acid solution and saline. The silyl ester group in the crude product is detached, at RT in 2 h, in a mixture consisting of 13.29 ml of methanol, 5.13 ml of THF, 5.13 ml of water and 904 mg of potassium carbonate. The mixture is concentrated down to half its volume on a RE at approximately 30° C., and the residue is diluted with ethyl acetate, and the organic phase is washed with 10% citric acid and saline (all being cold). The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and the residue is chromatographed on silica gel (eluent, hexane:ethyl acetate, 3:1 and 1:1), and the title compound is obtained. TLC Rf (hexane/ethyl acetate 2.5:1)=0.12. FAB-MS (M+H)+ =558.

Workup

  1. additionthe reaction solution is poured onto ice-water
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe organic phase is washed with 10% citric acid solution and saline
  4. waitThe silyl ester group in the crude product is detached, at RT in 2 h, in a mixture
  5. concentrationThe mixture is concentrated down to half its volume on a RE at approximately 30° C.
  6. additionthe residue is diluted with ethyl acetate
  7. washthe organic phase is washed with 10% citric acid and saline (all being cold)
  8. dry with materialThe combined organic phases are dried over sodium sulfate
  9. customthe residue is chromatographed on silica gel (eluent, hexane:ethyl acetate, 3:1 and 1:1)

Sources & evidence

ORD record
ord-067b5cb92eff42a9a19575c3af95d8fe
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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