Anisole → (5-Bromo-2-methylphenyl)(4-methoxyphenyl)methanone

HRID 1835676Notes

Reaction equation

HRID 1835676 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[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]([CH3:11])=[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 65578Oxalyl chlorideHCID 3460045-Bromo-2-methylbenzoic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 22328595(5-Bromo-2-methylphenyl)(4-methoxyphenyl)methanoneYield 90.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of Part A 5-bromo-2-methylbenzoic acid (43 g, 200 mmol) in 200 mL of CH2Cl2 containing oxalyl chloride (140 mL of a 2M CH2Cl2 solution) was added 0.25 mL of DMF. Once the vigorous evolution of gas ceased, the reaction was stirred 6 hr prior to removal of the volatiles using a rotary evaporator. After dissolving the crude 5-bromo-2-methylbenzoyl chloride in 150 ml of CS2, the resulting solution was cooled to 4° while stirring with an overhead stirrer prior to addition of anisole (21.6 g, 200 mmol) followed by AlCl3 (29.3 g, 220 mmol) in portions. The reaction, after warming to 20° over 1 hr, was stirred for 15 hr prior to quenching by pouring over ice/conc HCl. Subsequently, the suspension was diluted with 500 ml H2O and stirred until all solids were dissolved. 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 resulting tan solid was recrystallized from 95% EtOH to yield 55 g of 5-bromo-2-methyl-4′-methoxybenzophenone.

Workup

  1. customto removal of the volatiles
  2. customa rotary evaporator
  3. dissolutionAfter dissolving the crude 5-bromo-2-methylbenzoyl chloride in 150 ml of CS2
  4. temperaturethe resulting solution was cooled to 4°
  5. stirringwhile stirring with an overhead stirrer
  6. customThe reaction
  7. temperatureafter warming to 20° over 1 hr
  8. stirringwas stirred for 15 hr
  9. customto quenching
  10. additionby pouring over ice/conc HCl
  11. additionSubsequently, the suspension was diluted with 500 ml H2O
  12. stirringstirred until all solids
  13. dissolutionwere dissolved
  14. extractionThe mixture was extracted 3× with EtOAc
  15. washThe combined organic extracts were washed 1× with 1N HCl, H2O, aq NaHCO3, and brine
  16. dry with materialto drying over Na2SO4
  17. customAfter removal of the volatiles
  18. customthe resulting tan solid was recrystallized from 95% EtOH

Sources & evidence

ORD record
ord-05b31a6be24d4c2eacf3f9128168ac35
Source dataset
uspto-grants-2004_08
Patent number
US06774112B2

Reaction notes

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