Azobisisobutyronitrile → 4-Bromomethyl-2,3-difluoro-benzoic acid tert-butyl ester

HRID 79011Notes

Reaction equation

HRID 79011 reaction equation
[C:1]([O:5][C:6](=[O:16])[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([F:14])[C:8]=1[F:15])([CH3:4])([CH3:3])[CH3:2].[Br:17]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C.CC(OC)(C)C>C(Cl)(Cl)(Cl)Cl.C1CCCCC1>[C:1]([O:5][C:6](=[O:16])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][Br:17])=[C:9]([F:14])[C:8]=1[F:15])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 15413tert-Butyl methyl etherHCID 67184N-bromobutanimideHCID 57523122HCID 57523122, compound

Product 1

HCID 575231234-Bromomethyl-2,3-difluoro-benzoic acid tert-butyl esterYield 71.6%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 8078CyclohexaneSolvent

Procedure

A solution of 2,3-difluoro-4-methyl-benzoic acid tert-butyl ester (17.3 g, 75.9 mmol) and N-bromosuccinimide (13.5 g, 75.9 mmol) in carbon tetrachloride (250 mL) was degassed for 10 minutes. AIBN (1.2 g, 7.32 mmol) was added and the reaction mixture was stirred at reflux for 18 hours before being cooled to room temperature and filtered. The filtrate was concentrated in vacuo to give a residue which was subjected to flash chromatography (Si—PPC, gradient 0% to 10%, TBME in cyclohexane) to afford the title compound as a colourless oil (16.7 g, contaminated by 25% of starting material). 1H NMR (CDCl3, 400 MHz) 7.61 (1 H, ddd, J=8.3, 6.4, 2.1 Hz), 7.18 (1 H, ddd, J=8.1, 6.4, 1.8 Hz), 4.49 (2 H, d, J=1.3 Hz), 1.59 (9 H, s).

Workup

  1. temperatureat reflux for 18 hours
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto give a residue which

Sources & evidence

ORD record
ord-048a236568964962b72c40e1c07f9d32
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

Loading…