Imidazole → HCID 22874307, compound

HRID 263760Notes

Reaction equation

HRID 263760 reaction equation
[C:1]([NH:8][C@@H:9]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[C@@H:10]([OH:27])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:36]([Si:40]([CH3:43])([CH3:42])Cl)([CH3:39])([CH3:38])[CH3:37].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]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=1)[C@@H:10]([O:27][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][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 22874283HCID 22874283, compound

Product 1

HCID 22874307HCID 22874307, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Analogously to Example 1 j), 1.06 g of 5(S)-(Boc-amino)-4(S)-hydroxy-6-(p-fluorophenyl)-2(R)-(p-trifluoromethylphenylmethyl)-hexanoic acid in 2.3 ml of DMF are silylated with 1.47 g of tert-butyldimethylchlorosilane and 1.18 g of imidazole. Hydrolysis of the silyl ester function with 1.76 g of potassium carbonate in 50 ml of methanol/THF/water 3:1:1 yields, after column chromatography (SiO2, hexane/ethyl acetate 2: 1), the title compound: TLC Rf (D)=0.15; 1H-NMR (200 MHz, CD3OD): 7.59 and 7.39 (2d, 8 Hz, per 2 H), 7.19 and 6.98 (2 m, per 2 H), 6.47 and 5.90 (d, approximately 9 Hz, together 1 H), 3.9-3.65 (m, 2 H), 3.15-2.8 (m, 4 H), 2.53-2.37, 2.07-1.9 and 1.6-1.4 (3 m, per 1 H), 1.37-1.22 (m, 9 H), 0.94 (s, 9 H), 0.2-0.1 (m, 6 H).

Workup

  1. customyields

Sources & evidence

ORD record
ord-dbde1ce901a04e91a3bc5389d437fe73
Source dataset
uspto-grants-1997_07
Patent number
US05643878

Reaction notes

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