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

To a stirred suspension of 5-bromo-2-methylbenzoic acid (1.29 g, 6 mmol) in 12 mL of CH2Cl2 containing oxalyl chloride (8 mmol) was added 2 drops 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 15 ml of CS2, the stirred mixture was cooled to 4° prior to adding anisole (0.7 g, 6.6 mmol) followed by AlCl3 (1.7 g, 12 mmol). The reaction, after warming to 20° over 1 hr, was stirred for 15 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 resulting tan solid was recrystallized from 95% EtOH to yield 1.6 g of 5-bromo-2-methyl-4′-methoxybenzophenone.

1. customto removal of the volatiles
2. customa rotary evaporator
3. dissolutionAfter dissolving the crude 5-bromo-2-methylbenzoyl chloride in 15 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 15 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 resulting tan solid was recrystallized from 95% EtOH

ORD record

ord-f88def58143e4eae9e5487e01843af1a

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936590B2