Acetone → 7-Chloro-1-(2,3-dihydroxypropyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

HRID 1658444Notes

Reaction equation

HRID 1658444 reaction equation
C([N:4]1[C:10]2[CH:11]=[CH:12][C:13]([Cl:15])=[CH:14][C:9]=2[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])=[N:7][CH2:6][C:5]1=[O:23])C=C.[Mn]([O-])(=O)(=O)=[O:25].[K+].[CH3:30][C:31]([CH3:33])=[O:32]>>[Cl:15][C:13]1[CH:12]=[CH:11][C:10]2[N:4]([CH2:30][CH:31]([OH:32])[CH2:33][OH:25])[C:5](=[O:23])[CH2:6][N:7]=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[F:22])[C:9]=2[CH:14]=1

Participants

4

Reactant 3

HCID 180AcetoneHCID 516875Potassium PermanganateHCID 21529372HCID 21529372, compound

Product 1

HCID 30504337-Chloro-1-(2,3-dihydroxypropyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Procedure

33.0 g of 1-allyl-7-chloro-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one are dissolved in 300 ml of acetone. 16 g of potassium permanganate are dissolved in 300 ml of a buffer solution (sodium acetate/acetic acid buffer) and added dropwise at 10°C within 20 minutes and with stirring to the foregoing solution. After complete decolouration of the potassium permanganate solution, the mixture is filtered off under vacuum from the manganese dioxide, the manganese dioxide is washed with acetone and the residue is extensively freed from acetone on a rotary evaporator. The remaining aqueous solution is treated with equal portions of methanol, toluene and cyclohexane and partitioned by stirring well. The aqueous/ methanolic phase is then extensively freed from methanol on a rotary evaporator and the remaining aqueous phase is extracted with ethyl acetate. The ethyl acetate solution is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. The residue is brought to crystallization by seeding from a small amount of ethyl acetate. By recrystallization of the first crystalline product from ethyl acetate there is obtained pure 7-chloro-1-(2,3-dihydroxypropyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one of melting point 117°-118°C.

Workup

  1. additionadded dropwise at 10°C within 20 minutes
  2. filtrationAfter complete decolouration of the potassium permanganate solution, the mixture is filtered off under vacuum from the manganese dioxide
  3. washthe manganese dioxide is washed with acetone
  4. customthe residue is extensively freed from acetone on a rotary evaporator
  5. additionThe remaining aqueous solution is treated with equal portions of methanol, toluene and cyclohexane
  6. custompartitioned
  7. stirringby stirring well
  8. customThe aqueous/ methanolic phase is then extensively freed from methanol on a rotary evaporator
  9. extractionthe remaining aqueous phase is extracted with ethyl acetate
  10. washThe ethyl acetate solution is washed with saturated aqueous sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue is brought to crystallization
  15. customBy recrystallization of the first crystalline product from ethyl acetate

Sources & evidence

ORD record
ord-2b06b06013a64e32b49dbf177e536f07
Source dataset
uspto-grants-1976_06
Patent number
US03963777

Reaction notes

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