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

HRID 407747Notes

Reaction equation

HRID 407747 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 139b (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 139c (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-4f43c17065a349f5bd6ae64f301151ef
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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