1,4-Dibromobenzene → 4-Bromo-4'-methylbenzophenone

HRID 1747996Notes

Reaction equation

HRID 1747996 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1.CON(C)[C:17](=[O:25])[C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1>C1COCC1>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([C:17]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[O:25])=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 78041,4-DibromobenzeneHCID 5133773N-Methoxy-N,4-dimethylbenzamideHCID 178418339Butyllithium

Product 1

HCID 27570564-Bromo-4'-methylbenzophenoneYield 77.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of N,O-dimethylhydroxylamine hydrochloride (8.20 g) in THF (dry) (75 mL) was added TEA (23.4 mL) at 0° C. After being stirred at 0° C. for 20 min, 4-methylbenzoyl chloride (10 g) in THF (dry) (20 mL) was added to the reaction mixture. The mixture was stirred at room temperature for 2 days. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give N-methoxy-N, 4-dimethylbenzamide (11.7 g) as a yellow oil. n-Butyllithium (1.6 M in hexane) (25.1 mL) was added dropwise to a mixture of 1,4-dibromobenzene (8.29 g) in THF (dry) (105 mL) at −78° C. for 10 min. The mixture was stirred at the same temperature under nitrogen for 30 min to form white precipitates. A solution of N-methoxy-N, 4-dimethylbenzamide (6 g) in THF (dry) (20 mL) was added to the reaction mixture at −78° C. and the mixture was stirred at the same temperature under nitrogen for 30 min and then at room temperature under a dry atmosphere with anhydrous calcium chloride tube overnight. The mixture was quenched with sat. NH4Cl aq. at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (7.18 g) as a pale yellow solid.

Workup

  1. customto form white precipitates
  2. stirringthe mixture was stirred at the same temperature under nitrogen for 30 min
  3. customat room temperature
  4. customovernight
  5. customThe mixture was quenched with sat. NH4Cl aq. at room temperature
  6. extractionextracted with EtOAc
  7. customThe organic layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

Sources & evidence

ORD record
ord-7a0ee7023ddb4e2ebfa4cb83361e189d
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

Loading…