Imidazole → 1-(5-Bromo-2-fluorophenyl)-3-(tert-butyldimethylsilyloxy)-2,2-difluoropropan-1-ol

HRID 221772Notes

Reaction equation

HRID 221772 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:15])=[C:6]([CH:8]([OH:14])[C:9]([F:13])([F:12])[CH2:10][OH:11])[CH:7]=1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:15])=[C:6]([CH:8]([OH:14])[C:9]([F:13])([F:12])[CH2:10][O:11][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH:7]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 666662611-(5-Bromo-2-fluorophenyl)-2,2-difluoropropane-1,3-diol

Product 1

HCID 666654561-(5-Bromo-2-fluorophenyl)-3-(tert-butyldimethylsilyloxy)-2,2-difluoropropan-1-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of 1-(5-bromo-2-fluorophenyl)-2,2-difluoropropane-1,3-diol (17.0 g, 59.8 mmol) in dry DCM (200 mL) was added imidazole (12.2 g, 179.2 mmol) at 0° C. and stirred for 15 min. tert-butyldimethylsilylchloride (13.5 g, 89.5 mmol) was added to the resultant reaction mixture portion wise for a period of 30 min. and stirring continued for 2 h. Reaction was monitored by TLC analysis. The solids formed in the reaction mixture were separated by filtration and filtrate was concentrated under reduced pressure to obtain crude product which was purified by column chromatography on silica gel with 2% Ethylacetate in Hexane as eluent to furnish title compound as a colorless liquid. Yield=19 g (80%). TLC (20% ethyl acetate in Hexane): Rf=0.75),

Workup

  1. additionwas added to the resultant
  2. customreaction mixture portion wise for a period of 30 min.
  3. customReaction
  4. customThe solids formed in the reaction mixture
  5. customwere separated by filtration and filtrate
  6. concentrationwas concentrated under reduced pressure
  7. customto obtain crude product which
  8. customwas purified by column chromatography on silica gel with 2% Ethylacetate in Hexane as eluent

Sources & evidence

ORD record
ord-78ff1458a389472b900d27ef5fe85433
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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