N-bromobutanimide → Methyl 2-(bromomethyl)-3-fluorobenzoate

HRID 1261498Notes

Reaction equation

HRID 1261498 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[CH3:11].[Br:13]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[CH2:11][Br:13]

Participants

5

Reactant 2

HCID 67184N-bromobutanimide2×HCID 21752566Methyl 3-fluoro-2-methylbenzoate2×

Product 1

HCID 19788116Methyl 2-(bromomethyl)-3-fluorobenzoateYield 266.1%

Reagents, catalysts & solvents 2

HCID 7187Benzoyl PeroxideCatalyst2×HCID 5943Carbon TetrachlorideSolvent2×

Procedure

A solution of 3-fluoro-2-methyl-benzoic acid methyl ester (3.64 g, 21.67 mmol) in carbon tetrachloride (100 mL) was treated with N-bromosuccinimide (3.85 g, 21.63 mmol) and benzoyl peroxide (0.1 g). The reaction mixture was then heated at reflux temperature and after 3 h the heat was removed and it was stirred at room temperature over the weekend. The reaction was then filtered to remove the solids and concentrated in vacuo to yield a light yellow oil. The reaction was then repeated with the remaining 3-fluoro-2-methyl-benzoic acid methyl ester (6.1 g, 36.3 mmol) in carbon tetrachloride using N-bromosuccinimide (6.5 g, 36.5 mmol) and benzoyl peroxide (0.1 g) heating at reflux. The reaction mixture was then filtered and concentrated in vacuo. The two material from the two reactions was combined and purified by flash column chromatography (silica gel, 10% diethyl ether/hexanes) to afford 2-bromomethyl-3-fluoro-benzoic acid methyl ester (14.22 g, 99%) as a white solid.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux temperature
  3. customafter 3 h the heat was removed
  4. filtrationThe reaction was then filtered
  5. customto remove the solids
  6. concentrationconcentrated in vacuo
  7. customto yield a light yellow oil
  8. temperatureheating
  9. temperatureat reflux
  10. filtrationThe reaction mixture was then filtered
  11. concentrationconcentrated in vacuo
  12. custompurified by flash column chromatography (silica gel, 10% diethyl ether/hexanes)

Sources & evidence

ORD record
ord-6410d2b0beba4db89b3bb8003181f701
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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