Anisole → (5-Bromo-2-chloro-phenyl)-(4-ethoxy-phenyl)-methanone

HRID 586128Notes

Reaction equation

HRID 586128 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[C:18]1([O:24][CH3:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([C:21]1[CH:22]=[CH:23][C:18]([O:24][CH3:25])=[CH:19][CH:20]=1)=[O:9]

Participants

7

Reactant 4

HCID 7519AnisoleHCID 331275-Bromo-2-chlorobenzoic acidHCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 22328608(5-Bromo-2-chloro-phenyl)-(4-ethoxy-phenyl)-methanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of commercial 5-bromo-2-chlorobenzoic acid (506 mg, 2.12 mmol) in 10 mL of CH2Cl2 containing oxalyl chloride (2.4 mmol) was added 2 drops of DMF. Once the vigorous evolution of gas ceased, the reaction was stirred 1.5 hr prior to removal of the volatiles using a rotary evaporator. After dissolving the crude 5-bromo-2-chlorobenzoyl chloride in 8 ml of CS2, the stirred mixture was cooled to 4° prior to adding anisole (240 mg, 2.12 mmol) followed by AlCl3 (566 mg, 4.25 mmol). The reaction, after warming to 20° over 1 hr, was stirred for 20 hr prior to quenching with 1N HCl. Subsequently, the suspension was diluted with 50 ml H2O and stirred until all solids were in solution. The mixture was extracted 3× with EtOAc. The combined organic extracts were washed 1× with 1N HCl, H2O, aq NaHCO3, and brine prior to drying over Na2SO4. After removal of the volatiles, the residue was chromatographed on silica gel using 15% EtOAc/hexane to elute 450 mg of 5-bromo-2-chloro-4′-methoxybenzophenone.

Workup

  1. customto removal of the volatiles
  2. customa rotary evaporator
  3. dissolutionAfter dissolving the crude 5-bromo-2-chlorobenzoyl chloride in 8 ml of CS2
  4. temperaturethe stirred mixture was cooled to 4°
  5. customThe reaction
  6. temperatureafter warming to 20° over 1 hr
  7. stirringwas stirred for 20 hr
  8. customto quenching with 1N HCl
  9. additionSubsequently, the suspension was diluted with 50 ml H2O
  10. stirringstirred until all solids
  11. extractionThe mixture was extracted 3× with EtOAc
  12. washThe combined organic extracts were washed 1× with 1N HCl, H2O, aq NaHCO3, and brine
  13. dry with materialto drying over Na2SO4
  14. customAfter removal of the volatiles
  15. customthe residue was chromatographed on silica gel using 15% EtOAc/hexane
  16. washto elute 450 mg of 5-bromo-2-chloro-4′-methoxybenzophenone

Sources & evidence

ORD record
ord-3ef03d1198bf48feab698b23ea16ce54
Source dataset
uspto-grants-2005_08
Patent number
US06936590B2

Reaction notes

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