Imidazole → (2R,4S,5S)-2-benzyl-5-t-butoxycarbonylamino-4-t-butyldimethylsiloxy-6-phenylhexanoic acid

HRID 1585330Notes

Reaction equation

HRID 1585330 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@@H:10]([OH:23])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][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:36]([Si:40]([CH3:43])([CH3:42])Cl)([CH3:39])([CH3:38])[CH3:37]>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@@H:10]([O:23][Si:40]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:43])[CH3:42])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[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 99791245(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid

Product 1

HCID 11341508(2R,4S,5S)-2-benzyl-5-t-butoxycarbonylamino-4-t-butyldimethylsiloxy-6-phenylhexanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6.35 g of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid in 90 ml of DMF is treated, while being stirred, with 8 g of imidazole and 10 g of t-butyldimethylchlorosilane. After having been stirred at RT for 18 h, the yellow, clear solution is poured onto ice-water, and this mixture is extracted three times with 250 ml of ethyl acetate on each occasion. The combined extracts are washed, in succession, three times with 10% citric acid, once with water, three times with aqueous, saturated sodium bicarbonate solution, once with water and, finally, with saline. After drying over sodium sulfate, the solvent is evaporated and the resulting tert-butyl dimethylsilyl ether (13.5 g) is dissolved in 53 ml of THF and treated with 53 ml of acetic acid and 20 ml of water. After having been stirred at RT for 3 h, the mixture is poured onto water, and this mixture is extracted three times with ether. The collected ether extracts are washed twice with water and once with saline and dried over sodium sulfate. After concentrating, the crude product is purified by column chromatography (SiO2, hexane/ethyl acetate: 3.5/1.5), and the title compound is obtained. TLC Rf (D)=0.37; FAB-MS (M+H)+ =528.

Workup

  1. additionthe yellow, clear solution is poured onto ice-water
  2. extractionthis mixture is extracted three times with 250 ml of ethyl acetate on each occasion
  3. washThe combined extracts are washed, in succession, three times with 10% citric acid, once with water, three times with aqueous, saturated sodium bicarbonate solution
  4. dry with materialAfter drying over sodium sulfate
  5. customthe solvent is evaporated
  6. dissolutionthe resulting tert-butyl dimethylsilyl ether (13.5 g) is dissolved in 53 ml of THF
  7. additiontreated with 53 ml of acetic acid and 20 ml of water
  8. stirringAfter having been stirred at RT for 3 h
  9. additionthe mixture is poured onto water
  10. extractionthis mixture is extracted three times with ether
  11. washThe collected ether extracts are washed twice with water and once with saline
  12. dry with materialdried over sodium sulfate
  13. concentrationAfter concentrating
  14. customthe crude product is purified by column chromatography (SiO2, hexane/ethyl acetate: 3.5/1.5)

Sources & evidence

ORD record
ord-3b64c23c2fd14867b170e990985b34dc
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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