4-Toluenesulfonyl chloride → 6,6-Dimethyl-2-nitro-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine

HRID 1412108Notes

Reaction equation

HRID 1412108 reaction equation
O[CH2:2][C:3]1[N:7]([CH2:8][C:9]([CH3:12])([OH:11])[CH3:10])[N:6]=[C:5]([N+:13]([O-:15])=[O:14])[CH:4]=1.[H-].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[Cl-].[NH4+]>CN(C=O)C>[CH3:10][C:9]1([CH3:12])[O:11][CH2:2][C:3]2=[CH:4][C:5]([N+:13]([O-:15])=[O:14])=[N:6][N:7]2[CH2:8]1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 866840171-(5-(Hydroxymethyl)-3-nitro-1H-pyrazol-1-yl)-2-methylpropan-2-ol

Product 1

HCID 866840186,6-Dimethyl-2-nitro-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazineYield 22.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 330e (1.1 g, 5.1 mmol) in DMF (10 mL), was added NaH (60 percent dispersion in mineral oil, 246 mg, 6.14 mmol) at 0° C. The resulting suspension was stirred for 30 min, followed by the addition of p-toluenesulfonyl chloride (1169 mg, 6.14 mmol). The mixture was stirred at 60° C. overnight. After cooling to room temperature, saturated ammonium chloride solution was added and the mixture was extracted with dichloromethane. The combined organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate gradient (9:1 to 2:1) to afford 330f (228 mg, 22%). MS-ESI: [M+H]+ 198.3

Workup

  1. stirringThe mixture was stirred at 60° C. overnight
  2. extractionthe mixture was extracted with dichloromethane
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated under reduced pressure
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with petroleum ether/ethyl acetate gradient (9:1 to 2:1)

Sources & evidence

ORD record
ord-d523c703e4374f45afe2f57481adb2af
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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