Imidazole → (4-(5-Bromo-2-chlorobenzyl)phenoxy)(tert-butyl)dimethylsilane

HRID 625832Notes

Reaction equation

HRID 625832 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.N1C=CN=C1.[C:22]([Si:26](Cl)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23]>CN(C)C=O.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][Si:26]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:28])[CH3:27])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 574237514-((5-Bromo-2-chlorophenyl)methyl)phenol

Product 1

HCID 59747702(4-(5-Bromo-2-chlorobenzyl)phenoxy)(tert-butyl)dimethylsilaneYield 99.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(5-bromo-2-chloro-benzyl)-phenol (9.01 g, 30.28 mmol) dissolved in N,N-dimethylformamide (100 mL) and cooled to 0 degrees Celsius (ice bath) was added imidazole (4.53 g, 66.6 mmol) and 4-dimethylaminopyridine (370 mg, 3.03 mmol). tert-butylchlorodimethylsilane (6.85 g, 45.4 mmol) was added and the ice bath was removed. The reaction mixture was allowed to stir at room temperature overnight (˜16 hours), water (400 mL) was added and the resulting mixture was extracted with ethyl acetate (200 mL). The aqueous layer was extracted two additional times with ethyl acetate (200 mL). The combined organic layers were washed with water (200 mL), brine (200 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (120 g silica gel column) and eluting with a gradient of 0 to 50% ethyl acetate in heptane. 12.4 g (99% yield) of product obtained as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 0.18 (s, 6H), 0.97 (s, 9H), 3.96 (s, 2H), 6.77 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H), 7.17-7.30 (m, 3H).

Workup

  1. temperaturecooled to 0 degrees Celsius (ice bath)
  2. customthe ice bath was removed
  3. additionwas added
  4. extractionthe resulting mixture was extracted with ethyl acetate (200 mL)
  5. extractionThe aqueous layer was extracted two additional times with ethyl acetate (200 mL)
  6. washThe combined organic layers were washed with water (200 mL), brine (200 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (120 g silica gel column)
  11. washeluting with a gradient of 0 to 50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-34346d8a614b4ee0af61f899e417590d
Source dataset
uspto-grants-2016_04
Patent number
US09308204B2

Reaction notes

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