6-Oxabicyclo[3.1.0]hexane → 6-cyano-3,4-dihydro-2,2-dimethyl-4-(2-hydroxycyclopentan-1-yl)-2H-1,4-benzoxazine

HRID 37119

Reaction equation

HRID 37119 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH2:9][NH:8][C:7]=2[CH:14]=1)#[N:2].[H-].[Na+].[CH:17]12[O:22][CH:18]1[CH2:19][CH2:20][CH2:21]2>CN(C)C=O.O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:12])([CH3:13])[CH2:9][N:8]([CH:17]3[CH2:21][CH2:20][CH2:19][CH:18]3[OH:22])[C:7]=2[CH:14]=1)#[N:2]

Participants

6

Reactant 3

HCID 92446-Oxabicyclo[3.1.0]hexaneHCID 24758Sodium hydrideHCID 105356226-cyano-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazine

Product 1

HCID 199345646-cyano-3,4-dihydro-2,2-dimethyl-4-(2-hydroxycyclopentan-1-yl)-2H-1,4-benzoxazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

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.

Workup

  1. temperatureafter cooling to room temperature
  2. stirringThe mixture was stirred at 70° C. for 3 hours
  3. temperatureto cool
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with water and aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel column chromatography
  9. customthe resulting crude crystals were recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-658be5a07e2c441eb1bd87c04cd5b359
Source dataset
uspto-grants-1995_05
Patent number
US05420126

Linked notes

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