Dimethyl Sulfate → 3-Methyl Flunitrazepam

HRID 1155111Notes

Reaction equation

HRID 1155111 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-e3044b9419f34ae9a9f8201247d5f800
Source dataset
uspto-grants-1981_11
Patent number
US04299767

Reaction notes

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