Imidazole → Benzene, 1,5-difluoro-2-methyl-4-[[tris(1-methylethyl)silyl]oxy]-

HRID 1771735Notes

Reaction equation

HRID 1771735 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH3:9])=[CH:4][C:3]=1[OH:10].N1C=CN=C1.[CH3:16][CH:17]([Si:19](Cl)([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH3:18].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH3:9])=[CH:4][C:3]=1[O:10][Si:19]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:18])[CH3:16]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 139400Triisopropylsilyl chlorideHCID 84648928Phenol, 2,4-difluoro-5-methyl-

Product 1

HCID 89443589Benzene, 1,5-difluoro-2-methyl-4-[[tris(1-methylethyl)silyl]oxy]-Yield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2,4-difluoro-5-methylphenol (780 mg, 5.41 mmol, 1.0 eq) and imidazole (442 mg, 6.5 mmol, 1.2 eq) in DMF (10 mL) at 0° C. was added TIPSCl (1.15 g, 5.95 mmol, 1.1 eq) dropwise. After the addition, the reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was then poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give a crude residue, which was purified by column chromatography (petroleum ether: EtOAc, 100:1) to give the title compound as a colorless oil (1.2 g, 80%).

Workup

  1. additionAfter the addition
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto give a crude residue, which
  8. customwas purified by column chromatography (petroleum ether: EtOAc, 100:1)

Sources & evidence

ORD record
ord-673ef78312ad46849abe535ceff81b24
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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