Benzoyl Peroxide → methyl 3-(bromomethyl)-5-fluorobenzoate

HRID 1426291Notes

Reaction equation

HRID 1426291 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:13][CH2:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([F:1])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 44203100Benzoic acid, 3-fluoro-5-methyl-, methyl ester

Product 1

HCID 58938186methyl 3-(bromomethyl)-5-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

To a solution of methyl 3-fluoro-5-methylbenzoate (1.64 g, 9.75 mmol, from Step 1) and N-bromosuccinimide (2.05 g, 11.5 mmol) in carbon tetrachloride (20 mL) was added benzoyl peroxide (0.1 g, 0.6 mmol) and the mixture was heated to reflux for four hours. The reaction was then cooled to room temperature, filtered, and diluted with DCM. The solution was washed successively with sodium thiosulfate, 1N NaOH, water, and brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography, eluting with a gradient from 0-20% ethyl acetate in hexanes, afforded a partially purified product. The cleanest fractions were used in the displacement with amine in Step 3. 1H NMR (300 MHz, CDCl3): δ 7.87-7.85 (m, 1H), 7.68-7.62 (m, 1H), 7.31 (ddd, 1H), 4.47 (s, 2H), 3.93 (s, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for four hours
  3. filtrationfiltered
  4. additiondiluted with DCM
  5. washThe solution was washed successively with sodium thiosulfate, 1N NaOH, water, and brine
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated
  9. washFlash chromatography, eluting with a gradient from 0-20% ethyl acetate in hexanes
  10. customafforded a partially purified product

Sources & evidence

ORD record
ord-644a201f64ee41f8a06b4bcca542ce76
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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