Chlorotrimethylsilane → Methyl 2-bromo-2-(4-fluorophenyl)acetate

HRID 2252652Notes

Reaction equation

HRID 2252652 reaction equation
[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].C[Si](Cl)(C)C.[Br:28]Br>C1COCC1>[CH3:1][O:2][C:3](=[O:12])[CH:4]([Br:28])[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 24408BromineHCID 2733233Methyl 2-(4-fluorophenyl)acetateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 12717580Methyl 2-bromo-2-(4-fluorophenyl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Fluorophenylacetic acid methyl ester (3.0 g, 17.6 mmol) in THF (20 mL) under nitrogen at −78° was treated with 1M lithium hexamethyldisilazide (19.4 mL, 19.4 mmol) and stirred at −78° for fifteen minutes. Trimethyl silyl chloride was added (2.23 mL, 17.6 mmol) and the reaction stirred for a further fifteen minutes. Bromine (0.9 mL, 17.6 mmol) was added and the reaction stirred again for a further fifteen minutes then quenched with water and partitioned between DCM and sodium hydrogen carbonate solution. The organic phase was separated, dried (sodium sulphate) and concentrated in vacuo. Flash chromatography (diethylether-silica) yielded the title compound.

Workup

  1. stirringthe reaction stirred for a further fifteen minutes
  2. stirringthe reaction stirred again for a further fifteen minutes
  3. customthen quenched with water
  4. custompartitioned between DCM and sodium hydrogen carbonate solution
  5. customThe organic phase was separated
  6. dry with materialdried (sodium sulphate)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a97461835d441fd8fb7f0d7c610173c
Source dataset
uspto-grants-2008_01
Patent number
US07323464B2

Reaction notes

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