Water → Benzyl 3-bromo-4-cyanobenzoate

HRID 906049Notes

Reaction equation

HRID 906049 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]#[N:12])[C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>CC(C)=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]#[N:12])[C:5]([O:7][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:6]

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl Bromide2×HCID 10796Cesium carbonateHCID 534255203-Bromo-4-cyanobenzoic acid

Product 1

HCID 67404157Benzyl 3-bromo-4-cyanobenzoateYield 45.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-4-cyanobenzoic acid (1.51 g, 6.69 mmol) in acetone (30 mL) was added cesium carbonate (4.4 g, 13.4 mmol) and benzyl bromide (790 uL, 6.69 mmol). The mixture was stirred at reflux for 15 hours at which point additional benzyl bromide was added (200 uL, 1.68 mmol). The mixture was stirred at reflux for a further 2 h and was then cooled to room temperature. Water and ethyl acetate were added and the layers were separated. The aqueous phase was then saturated with lithium chloride and extracted with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (4:1 hexanes:ethyl acetate) to provide phenylmethyl 3-bromo-4-cyanobenzoate (957 mg, 3.03 mmol, 45% yield) as a yellow orange oil that slowly solidified. 1H NMR (400 MHz, CDCl3): 8.35 (d, 1H), 8.09 (dd, 1H), 7.73 (d, 1H), 7.46-7.35 (m, 5H), 5.35 (s, 2H).

Workup

  1. additionwas added (200 uL, 1.68 mmol)
  2. stirringThe mixture was stirred
  3. temperatureat reflux for a further 2 h
  4. customthe layers were separated
  5. extractionsaturated with lithium chloride and extracted with ethyl acetate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-538b32aea86249d9a40e58734e2d42f4
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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