N-bromobutanimide → Methyl 4-bromo-2-(bromomethyl)benzoate

HRID 63480Notes

Reaction equation

HRID 63480 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][C:5]=1[CH3:11].[Br:13]N1C(=O)CCC1=O>C(#N)C.S(=O)(O)[O-].[Na+].CCOCC.CC(N=NC(C#N)(C)C)(C#N)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][C:5]=1[CH2:11][Br:13]

Participants

7

Reactant 2

HCID 67184N-bromobutanimideHCID 22031226Methyl 4-bromo-2-methylbenzoate

Product 1

HCID 22031079Methyl 4-bromo-2-(bromomethyl)benzoateYield 66.2%

Reagents, catalysts & solvents 4

HCID 6547AzobisisobutyronitrileCatalystHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 23665763Sodium BisulfiteSolvent

Procedure

A mechanically stirred mixture of 4-bromo-2-methyl-benzoic acid methyl ester (115 g, 500 mmol), N-bromosuccinimide (90 g, 500 mmol) and AIBN (3.1 g) in acetonitrile (700 mL) was warmed over 45 minutes to a gentle reflux, and held at reflux for 21 hours. The reaction mixture was cooled to room temperature, diluted with saturated aqueous sodium bisulfite, and concentrated in vacuo. The residue was partitioned between water and 1:1 hexanes:ethyl acetate. The organic phase was washed with water, brine, and filtered through a pad of silica gel. The solvent was removed under vacuum to give an oil/solid mixture, which was digested in ether and filtered. The filtrate was chromatographed on silica gel using a hexanes-ethyl acetate gradient, eluting the product at 4:1 hexanes-ethyl acetate and providing 102 g of 4-bromo-2-bromomethyl-benzoic acid methyl ester, in 66% yield; 1H NMR (DMSO-d6) δ 3.87 (s, 3H), 4.99 (s, 2H), 7.67-7.97 (m, 3H).

Workup

  1. temperaturewas warmed over 45 minutes to a gentle reflux
  2. temperatureat reflux for 21 hours
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and 1:1 hexanes
  5. washThe organic phase was washed with water, brine
  6. filtrationfiltered through a pad of silica gel
  7. customThe solvent was removed under vacuum
  8. customto give an oil/solid mixture, which
  9. filtrationfiltered
  10. customThe filtrate was chromatographed on silica gel using a hexanes-ethyl acetate gradient
  11. washeluting the product at 4:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-2f764d7f0afb4b2b96e12d28607d05df
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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