Hydrochloric Acid → 2-Bromo-7,9-dihydroxy-10,11-dihydrodibenz[b,f]oxepin-10-one

HRID 48007

Reaction equation

HRID 48007 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4](Cl)[CH:3]=1.C[O:13][C:14]1[CH:15]=[C:16]([OH:22])[CH:17]=[C:18]([O:20][CH3:21])[CH:19]=1.C(=O)([O-])[O-].[K+].[K+].Cl>[Cu].[Cu]I.C(OCC)(=O)C.C1C=CC=CC=1.CN1CCCC1=O>[Br:1][C:2]1[CH:10]=[CH:9][C:21]2[O:20][C:18]3[CH:19]=[C:14]([OH:13])[CH:15]=[C:16]([OH:22])[C:17]=3[C:6](=[O:7])[CH2:5][C:4]=2[CH:3]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 103833,5-DimethoxyphenolHCID 11430Potassium CarbonateHCID 1088294-Bromo-2-chlorobenzoic acid

Product 1

HCID 234318462-Bromo-7,9-dihydroxy-10,11-dihydrodibenz[b,f]oxepin-10-oneYield 62.6%

Reagents, catalysts & solvents 5

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 241BenzeneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 88.3 g (F.W. 235.46, 375 mmol) of 4-bromo-2-chlorobenzoic acid (3), 57.8 g (F.W. 154.165, 375 mmol) of 3,5-dimethoxyphenol (13), 93.2 g (F.W. 138.21, 670 mmol) of potassium carbonate and 400 mL of N-methyl-2-pyrrolidone was added benzene (200 mL), and the resulting solution was dried by a Dean-Stark water separator (140-170° C.) for three hours and then, 6.0 g (F.W. 63.55, 93.7 mmol) of copper (powder) and 17.8 g (F.W. 190.45, 93.7 mmol) of copper (I) iodide were added thereto and stirred at 120° C. for 30 minutes. This reaction mixture was cooled by standing and ice water and ethyl acetate were added thereto and then, the obtained solution was made pH 2 with concentrated hydrochloric acid and filtered. The organic layer was separated and then, thoroughly washed with water and subjected to salting out with a saturated sodium chloride aqueous solution. The resulting solution was dried with anhydrous magnesium sulfate and concentrated and the residue was purified by silica gel column chromatography (developing solvent; ethyl acetate:hexane=1:3) and recrystallized from ethyl acetate-hexane to obtain 75.4 g (57%) a desired compound (20). (TLC; ethyl acetate:hexane=1:2 or 1:1).

Workup

  1. dry with materialthe resulting solution was dried by a Dean-Stark water separator (140-170° C.) for three hours
  2. temperatureThis reaction mixture was cooled
  3. filtrationfiltered
  4. customThe organic layer was separated
  5. washthoroughly washed with water
  6. dry with materialThe resulting solution was dried with anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customthe residue was purified by silica gel column chromatography (developing solvent; ethyl acetate:hexane=1:3)
  9. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-a5b93d68da6448919b73cc4727d101dc
Source dataset
uspto-grants-2004_03
Patent number
US06700013B2

Linked notes

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