Imidazole → 5(s)-(Boc-amino)-4(s)-(tert-butyldimethylsilyloxy)-6-(p-methoxyphenyl)-2(r)-(phenylmethyl)hexanoic acid

HRID 1377149Notes

Reaction equation

HRID 1377149 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[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].[C:33]([Si:37]([CH3:40])([CH3:39])Cl)([CH3:36])([CH3:35])[CH3:34].N1C=CN=C1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCCCC.C(OCC)(=O)C.O.C1COCC1>[C:1]([NH:8][C@@H:9]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[C@@H:10]([O:23][Si:37]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:40])[CH3:39])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 228764105(s)-(Boc-amino)-4(s)-hydroxy-6-(p-methoxyphenyl)-2(r)-(phenylmethyl)hexanoic acid

Product 1

HCID 228764245(s)-(Boc-amino)-4(s)-(tert-butyldimethylsilyloxy)-6-(p-methoxyphenyl)-2(r)-(phenylmethyl)hexanoic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

2.9 g (6.54 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-(p-methoxyphenyl)-2(R)-(phenylmethyl)hexanoic acid in 7 ml of DMF are silylated, at RT for 20 h and under an N2 atmosphere, with 4.5 g (30 mmol) of tert-butyldimethylchlorosilane and 3.65 g (53.6 mmol) of imidazole. 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. Hydrolysis of the residue in 80 ml of methanol and 30 ml of THF with 5.4 g of potassium carbonate and 30 ml of water, working up after 3 h in analogy with Example 7c), and column chromatography (SiO2, hexane/ethyl acetate, 2:1), affords the title compound: TLC Rf (D)=0.13; tRet (II)=20.3 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. customHydrolysis of the residue in 80 ml of methanol

Sources & evidence

ORD record
ord-d96b61fe18764bfc909d5f60df606782
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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