Reaction #65397

Reaction equation

sodium hydride

6-cyano-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazine

cyclopentene oxide

→

6-cyano-3,4-dihydro-4-(2-hydroxycyclopentan-1-yl)-2,2-dimethyl-2H-1,4-benzoxazine

Solvents

N,N-dimethylformamide

water

Conditions

Workup

1. 1
   Temperatureafter cooling to room temperature
2. 2
   workup.STIRRINGThe mixture was stirred at 70° C. for 3 hours
3. 3
   Temperatureto cool
4. 4
   Extractionextracted with ethyl acetate
5. 5
   WashThe extract was washed with water and aqueous sodium chloride solution
6. 6
   Dryingdried over anhydrous magnesium sulfate
7. 7
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
8. 8
   OtherThe residue was purified by silica gel column chromatography
9. 9
   Otherthe resulting crude crystals were recrystallized from ethyl acetate-hexane

Procedure

In 20 ml of N,N-dimethylformamide was dissolved 1.0 g of 6-cyano-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazine followed by addition of 0.24 g of sodium hydride. The mixture was stirred at 70° C. for 1 hour and after cooling to room temperature, 0.5 ml of cyclopentene oxide was added. The mixture was stirred at 70° C. for 3 hours. The reaction mixture was then allowed to cool, diluted with water and extracted with ethyl acetate. The extract was washed with water and aqueous sodium chloride solution and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography and the resulting crude crystals were recrystallized from ethyl acetate-hexane to give 0.53 g of 6-cyano-3,4-dihydro-4-(2-hydroxycyclopentan-1-yl)-2,2-dimethyl-2H-1,4-benzoxazine.

Source