Dimethylformamide → 2,3-Dihydro-1-benzoxepine-4-carboxamide

HRID 565942Notes

Reaction equation

HRID 565942 reaction equation
CC1C=CC([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=CC=1.C(Cl)(=O)C(Cl)=O.C[N:29](C)C=O>ClCCl>[O:17]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:21][C:12]=2[CH:13]=[C:14]([C:18]([NH2:29])=[O:19])[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acid

Product 1

HCID 184723002,3-Dihydro-1-benzoxepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.15g) in dichloromethane (6ml) were added oxalyl chloride (0.14ml) and dimethylformamide (catalytic amount) under ice-cooling, and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran. The mixture was dropwise added to a solution of 4-((N-(3,5-dimethylcyclohexyl)-N-methyl)-aminomethyl)aniline (0.13g) and triethylamine (0.23ml) in tetrahydrofuran (10ml), under ice-cooling. Under nitrogen atmosphere, the mixture was stirred at room temperature over night. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated to give crude crystals, which were recrystallized from diethyl ether-hexane to give N-(4-((N-methyl-N-(3,5-dimethylcyclohexyl))aminomethyl)-phenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 133) (0.22g) as colorless crystals.

Workup

  1. temperaturecooling
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in tetrahydrofuran
  4. additionThe mixture was dropwise added to a solution of 4-((N-(3,5-dimethylcyclohexyl)-N-methyl)-aminomethyl)aniline (0.13g) and triethylamine (0.23ml) in tetrahydrofuran (10ml), under ice-
  5. temperaturecooling
  6. stirringUnder nitrogen atmosphere, the mixture was stirred at room temperature over night
  7. customThe solvent was evaporated
  8. additionto the residue was added water
  9. extractionThe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and saturated sodium chloride solution
  11. dry with materialdried with anhydrous magnesium sulfate
  12. customUnder reduced pressure, the solvent was evaporated
  13. customto give crude crystals, which
  14. customwere recrystallized from diethyl ether-hexane

Sources & evidence

ORD record
ord-7b31fb6797cf4ef2bbf8f5db8d4674fa
Source dataset
uspto-grants-2001_01
Patent number
US06172061B2

Reaction notes

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