2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole → 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol

HRID 1627289Notes

Reaction equation

HRID 1627289 reaction equation
[Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:43]=[C:42]([F:44])[C:15]([CH2:16][S:17][C:18]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:20]([C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([O:33][CH3:34])[CH:27]=3)([CH3:25])[CH3:24])=[CH:21][N:22]=2)=[C:14]([F:45])[CH:13]=1)(C(C)(C)C)(C)C>CC#N>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]([C:20]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:18]([S:17][CH2:16][C:15]3[C:14]([F:45])=[CH:13][C:12]([O:11][CH2:10][CH2:9][OH:8])=[CH:43][C:42]=3[F:44])=[N:22][CH:21]=2)([CH3:25])[CH3:24])=[CH:27][C:28]=1[O:33][CH3:34]

Participants

3

Reactant 1

HCID 667406352-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

Product 1

HCID 667407372-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanolYield 95%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole in CH3CN (1 mL) was added a 5% solution of aqueous HF in CH3CN (3 mL). The reaction was complete in 1 h and the crude product was extracted with EtOAc (3×75 mL). The combined extracts were washed with H2O and brine, and dried over anhyd Na2SO4, concentrated and purified by flash chromatography (20% MeOH/DCM) to yield the title compound (493 mg, 95%) as a white solid. MS (EI) m/z 563.30 (MH+).

Workup

  1. extractionthe crude product was extracted with EtOAc (3×75 mL)
  2. washThe combined extracts were washed with H2O and brine
  3. dry with materialdried over anhyd Na2SO4
  4. concentrationconcentrated
  5. custompurified by flash chromatography (20% MeOH/DCM)

Sources & evidence

ORD record
ord-f8593d3047ac424594bb12bebd266ff3
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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