Imidazole → 4-((Tert-butyldimethylsilyl)oxy)-2-fluorobenzonitrile

HRID 1678702Notes

Reaction equation

HRID 1678702 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].N1C=CN=C1.[CH3:16][C:17]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Si:20]([O:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1)([C:17]([CH3:19])([CH3:18])[CH3:16])([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 27346752-Fluoro-4-hydroxybenzonitrile

Product 1

HCID 593707824-((Tert-butyldimethylsilyl)oxy)-2-fluorobenzonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-Fluoro-4-hydroxybenzonitrile (30.1 g; manufactured by Wako Pure Chemical Industries, Ltd.) and imidazole (18.3 g; manufactured by Tokyo Chemical Industry Co., Ltd.) were dissolved in dehydrated DMF (436 mL; manufactured by Kanto Chemical Co., Inc.), and the solution was cooled to 0° C. Subsequently, TBDMSCl (48.3 g; manufactured by Tokyo Chemical Industry Co., Ltd.) was added thereto, and the mixture was stirred for one hour while the temperature was raised to room temperature. The solvent was evaporated under reduced pressure from the reaction solution, subsequently water was added thereto, and the mixture was extracted two times with ethyl acetate. The organic layer was washed two times with water and with brine, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by column chromatography (“COLUMN-A.”; n-hexane:ethyl acetate=100:0→94:6). Thus, the title compound (40.3 g) was obtained.

Workup

  1. temperaturewas raised to room temperature
  2. customThe solvent was evaporated under reduced pressure from the reaction solution, subsequently water
  3. additionwas added
  4. extractionthe mixture was extracted two times with ethyl acetate
  5. washThe organic layer was washed two times with water
  6. dry with materialwith brine, and was dried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by column chromatography (“COLUMN-A.”; n-hexane:ethyl acetate=100:0→94:6)

Sources & evidence

ORD record
ord-d59687f4c8524911b17402b0c2ad2e5b
Source dataset
uspto-grants-2011_08
Patent number
US08008506B2

Reaction notes

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