Dimethyl Sulfate → 3-Methyl Flunitrazepam

HRID 848124Notes

Reaction equation

HRID 848124 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[O:22])[CH:10]([CH3:23])[N:9]=1.[C:24](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[N:12]([CH3:24])[C:11](=[O:22])[CH:10]([CH3:23])[N:9]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 20542078(+)-5-(o-fluorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one

Product 1

HCID 205623323-Methyl Flunitrazepam

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

95 g (0.30 M) of rac-5-(o-fluorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one are dissolved in 1 liter of absolute acetone and treated with 60 g of powdered potassium carbonate and 43 g of dimethyl sulphate. The mixture is stirred at room temperature for 4 hours and left to stand in a refrigerator for 48 hours. The mixture is then concentrated, treated with ice-water and extracted several times with methylene chloride. The organic solution is dried over sodium sulphate, filtered and concentrated. The residue is crystallised from ethyl acetate/petroleum ether, there being obtained rac-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-7-nitro-2H-1,4-benzodiazepin-2-one which melts at 154°-156° C.

Workup

  1. waitleft
  2. waitto stand in a refrigerator for 48 hours
  3. concentrationThe mixture is then concentrated
  4. additiontreated with ice-water
  5. extractionextracted several times with methylene chloride
  6. dry with materialThe organic solution is dried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is crystallised from ethyl acetate/petroleum ether, there

Sources & evidence

ORD record
ord-dd4eafacf81644cea594457d4abe3803
Source dataset
uspto-grants-1981_10
Patent number
US04294758

Reaction notes

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