Imidazole → (2-(4-Bromo-2,6-dimethylphenyl)-2,2-difluoroethoxy)(tert-butyl)dimethylsilane

HRID 708806Notes

Reaction equation

HRID 708806 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]([F:13])([F:12])[CH2:10][OH:11])=[C:4]([CH3:14])[CH:3]=1.N1C=CN=C1.[C:20]([Si:24]([CH3:27])([CH3:26])Cl)([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]([C:9]([F:12])([F:13])[CH2:10][O:11][Si:24]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:27])[CH3:26])=[C:6]([CH3:8])[CH:7]=1

Participants

7

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 1180986772-(4-Bromo-2,6-dimethylphenyl)-2,2-difluoroethanol

Product 1

HCID 123422069(2-(4-Bromo-2,6-dimethylphenyl)-2,2-difluoroethoxy)(tert-butyl)dimethylsilaneYield 66.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of Intermediate 7B (2.68 g, 10.11 mmol) and imidazole (1.376 g, 20.22 mmol) in DMF (30 ml) was added tert-butyl dimethylchlorosilane (1.828 g, 12.13 mmol). The mixture was stirred at rt overnight, diluted with EtOAc and sat. NaHCO3. The organic layer was extracted by EtOAc (3×20 ml). The combined organic layer was washed with water and brine, dried (MgSO4) and concentrated. The crude product was purified by flash chromatography to give Intermediate 7C (2.56 g, 66.8% yield) as a colorless oil. 1H NMR (400 MHz, chloroform-d) δ ppm −0.01 (s, 6H) 0.84 (s, 9H) 2.42 (t, J=4.61 Hz, 6H) 4.00 (t, J=13.18 Hz, 2H) 7.20 (s, 2H). 19F NMR (376 MHz, chloroform-d) δ ppm −95.94 (br. s., 2F).

Workup

  1. extractionThe organic layer was extracted by EtOAc (3×20 ml)
  2. washThe combined organic layer was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-bf8b2682ba1b4cc6890bdbfff6487432
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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