Reaction #1445

Reaction equation

oxalyl chloride

dimethylformamide

2-methoxybiphen-4-ylcarboxylic acid

5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine

→

1-(2'-methoxybiphen-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine

Solvents

water

dichloromethane

dichloromethane

triethylamine

Conditions

Workup

1. 1
   Temperaturewith cooling on an ice bath
2. 2
   Concentrationthe reaction solution was concentrated under a reduced pressure
3. 3
   workup.DISSOLUTIONThe thus obtained residue was dissolved in 8.4 ml of dichloromethane
4. 4
   Temperaturewith cooling on an ice bath
5. 5
   workup.ADDITIONthe resulting solution was dropwise added to a solution
6. 6
   Otherobtained
7. 7
   TemperatureThe reaction solution was warmed up to room temperature
8. 8
   OtherThe resulting reaction solution
9. 9
   Othersubjected to phase separation
10. 10
    Otherto separate dichloromethane layer which
11. 11
    Washwas subsequently washed with 0.5N hydrochloric acid
12. 12
    Dryinga saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate
13. 13
    OtherAfter removing the solvent
14. 14
    workup.DISTILLATIONby distillation
15. 15
    Otherthe thus obtained residue was crystallized from toluene

Procedure

A 1.67 g portion of 2-methoxybiphen-4-ylcarboxylic acid was dissolved in 17 ml of dichloromethane, 0.95 ml of oxalyl chloride and a catalytically effective amount of dimethylformamide were added to the resulting solution with cooling on an ice bath and then the resulting mixture was warmed up to room temperature. When completion of foaming was confirmed, the reaction solution was concentrated under a reduced pressure and subjected to azeotropic treatment with toluene twice. The thus obtained residue was dissolved in 8.4 ml of dichloromethane and, with cooling on an ice bath, the resulting solution was dropwise added to a solution obtained by dissolving 1.0 g of 5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine and 1.53 ml of triethylamine in 10 ml of dichloromethane. The reaction solution was warmed up to room temperature and the stirring was continued for 1 hour. The resulting reaction solution was mixed with water and subjected to phase separation to separate dichloromethane layer which was subsequently washed with 0.5N hydrochloric acid and a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate. After removing the solvent by distillation, the thus obtained residue was crystallized from toluene to obtain 1.65 g of 1-(2'-methoxybiphen-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine as crude crystals.

Source