Imidazole → 5(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-phenyl-2(R)-[(2,4-difluorophenyl)methyl]hexanoic acid

HRID 2394092Notes

Reaction equation

HRID 2394092 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][C:20]([F:23])=[CH:19][C:18]=1[F:24])[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.CO.C1COCC1.O.CCCCCC.C(OCC)(=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:37]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:40])[CH3:39])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

10

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 228742865(S)-(Boc-Amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-difluorophenyl)methyl]hexanoic acid

Product 1

HCID 228743095(S)-(Boc-Amino)-4(S)-(tert-butyldimethylsilyloxy)-6-phenyl-2(R)-[(2,4-difluorophenyl)methyl]hexanoic acid

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

In analogy with Example 1j), 3.2 g (7.12 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-difluorophenyl)methyl]hexanoic acid in 67 ml of DMF are silylated with 4.93 g (32.7 mmol) of tert-butyldimethylchlorosilane and 3.97 g (58.4 mmol) of imidazole. Hydrolysis of the silyl ester function with 5.9 g of potassium carbonate in 77 ml of methanol, 20 ml of THF and 20 ml of water yields the title compound after column chromatography (SiO2, hexane/ethyl acetate, 2:1): TLC Rf (D)=0.22; tRet (II)=20.8 min.

Sources & evidence

ORD record
ord-5a9d1d6ca36e4d529296cb14e68f2727
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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