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

HRID 1658445Notes

Reaction equation

HRID 1658445 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH:13]3[O:15][CH2:14]3)[C:10](=[O:16])[CH2:9][N:8]=[C:7]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])[C:6]=2[CH:24]=1.S(=O)(=O)(O)[OH:26].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH:13]([OH:26])[CH2:14][OH:15])[C:10](=[O:16])[CH2:9][N:8]=[C:7]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])[C:6]=2[CH:24]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 21529373HCID 21529373, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1 g of crude 7-chloro-1-(2,3-epoxypropyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one is dissolved in 15 ml of methanol and 15 ml of 2 N sulfuric acid and stirred for 1 hour at 25°C. Then the solution is made alkaline with 3 N sodium hydroxide and the methanol is carefully distilled on a rotary evaporator. The aqueous phase is extracted with ethyl acetate and the ethyl acetate solution is washed with water, dried over magnesium sulfate, filtered and concentrated. By chromatography of the residue on silica gel with ethyl acetate/methanol (9:1) there is isolated 7-chloro-1-(2,3-dihydroxypropyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one of melting point 116°-117°C.

Workup

  1. distillationthe methanol is carefully distilled on a rotary evaporator
  2. extractionThe aqueous phase is extracted with ethyl acetate
  3. washthe ethyl acetate solution is washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0a471012d8e14460ade654e6570ca200
Source dataset
uspto-grants-1976_06
Patent number
US03963777

Reaction notes

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