Azobisisobutyronitrile → 4-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 2048106Notes

Reaction equation

HRID 2048106 reaction equation
[F:1][C:2]1[CH:14]=[C:13]([CH3:15])[C:12]([F:16])=[CH:11][C:3]=1[C:4]([NH:6][S:7]([CH3:10])(=[O:9])=[O:8])=[O:5].[Br:17]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>ClCCCl>[Br:17][CH2:15][C:13]1[C:12]([F:16])=[CH:11][C:3]([C:4]([NH:6][S:7]([CH3:10])(=[O:8])=[O:9])=[O:5])=[C:2]([F:1])[CH:14]=1

Participants

5

Reactant 3

HCID 6547Azobisisobutyronitrile2×HCID 67184N-bromobutanimideHCID 666671302,5-difluoro-4-methyl-N-(methylsulfonyl)benzamide

Product 1

HCID 666671114-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamideYield 56%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A stirred mixture of 2,5-difluoro-4-methyl-N-(methylsulfonyl)benzamide (Preparation 244, 5.07 g, 20.3 mmol), N-bromosuccinimide (freshly recrystallised and dried, 4.71 g, 26.4 mmol) and azobisisobutyronitrile (0.05 g, 0.30 mmol) in 1,2-dichloroethane (100 mL) was heated at reflux under nitrogen whilst being irradiated with light from a lamp. After 2 hours, additional azobisisobutyronitrile (0.05 g, 0.30 mmol) was added and the reaction heated under reflux for 2 hours more. The reaction mixture was cooled to room temperature and evaporated in vacuo. The resulting residue was partitioned between brine (200 mL) and EtOAc (2×150 mL). The combine organic extracts were dried over magnesium sulphate and concentrated in vacuo to yield a pale yellow oil which solidified on standing (7.88 g). The solid was purified by silica gel chromatography eluting with 0 to 30% EtOAc in heptane to afford the title compound as a white solid (3.71 g, 56%):

Workup

  1. customfreshly recrystallised
  2. customdried
  3. temperatureat reflux under nitrogen
  4. customwhilst being irradiated with light from a lamp
  5. temperaturethe reaction heated
  6. temperatureunder reflux for 2 hours more
  7. customevaporated in vacuo
  8. customThe resulting residue was partitioned between brine (200 mL) and EtOAc (2×150 mL)
  9. dry with materialThe combine organic extracts were dried over magnesium sulphate
  10. concentrationconcentrated in vacuo
  11. customto yield a pale yellow oil which
  12. customThe solid was purified by silica gel chromatography
  13. washeluting with 0 to 30% EtOAc in heptane

Sources & evidence

ORD record
ord-a96b76fbfe9442cca2854b970bf42735
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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