Hydrochloric Acid → Ethyl 7-(4-tert-butylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate

HRID 1277178Notes

Reaction equation

HRID 1277178 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.COB(OC)OC.Cl.Br[C:26]1[CH:27]=[CH:28][C:29]2[O:35][CH2:34][CH2:33][C:32]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][C:30]=2[CH:41]=1.B([O-])([O-])OC1C=CC(C(C)(C)C)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)C.C1(C)C(CCO)=CC=CC=1.O.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:26]2[CH:27]=[CH:28][C:29]3[O:35][CH2:34][CH2:33][C:32]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][C:30]=3[CH:41]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 775951-Bromo-4-tert-butylbenzeneHCID 10709089HCID 10709089, compoundHCID 867561654-Tert-butylphenyl borateHCID 178418339Butyllithium

Product 1

HCID 18472239Ethyl 7-(4-tert-butylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylateYield 85.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 66602552Toluene-ethanol waterSolvent

Procedure

Under argon atmosphere, to a solution of 4-tert-butylbromobenzene (10.0 g) in diethylether (50 ml) was added n-butyllithium (1.6M, hexane solution) (32.3 ml) at -78° C., and the mixture was stirred for 1 hour. To the reaction mixture was dropwise added trimethyl boric acid (16 ml) in diethylether (30 ml), and the mixture was warmed to room temperature and stirred at room temperature 16 hours. To the reaction mixture were added 1N hydrochloric acid (50 ml) and water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:9) to give crude 4-tert-phenyl borate(0.84 g) as pale yellow oil. Under argon atmosphere, a solution of ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate (500 mg), the above crude 4-tert-butylphenyl borate(0.59 g) and potassium carbonate (0.47 g) in toluene-ethanol-water (20-2-2 ml) was stirred at room temperature for 1 hour. To the reaction mixture was added tetrakistriphenylphosphine palladium (0.06 g), and the mixture was refluxed for 20 hours and cooled to room temperature. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:19) to give ethyl 7-(4-tert-butyl-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate (504 mg) as colorless oil.

Workup

  1. stirringstirred at room temperature 16 hours
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was separated
  7. custompurified with column chromatography (ethyl acetate/hexane=1:9)
  8. customto give crude 4-tert-phenyl borate(0.84 g) as pale yellow oil
  9. temperaturethe mixture was refluxed for 20 hours
  10. temperaturecooled to room temperature
  11. washThe organic layer was washed with saturated sodium chloride solution
  12. dry with materialdried with magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was separated
  15. custompurified with column chromatography (ethyl acetate/hexane=1:19)

Sources & evidence

ORD record
ord-76a4b4d2c78d49e396efbe858fc97f41
Source dataset
uspto-grants-2000_12
Patent number
US06166006

Reaction notes

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