Sulfuric Acid → Estazolam

HRID 867066

Reaction equation

HRID 867066 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.[CH:21]([O-])([O-])OCC.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:21]=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 123908747-Chloro-2-hydrazinyl-5-phenyl-3H-1,4-benzodiazepineHCID 53630039Ethylorthoformate

Product 1

HCID 3261Estazolam

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 2.0 parts of 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine and 7.4 parts of ethyl orthoformate in 80 parts by volume of chloroform is added 2 parts of concentrated sulfuric acid with stirring. The mixture is stirred at room temperature for further 30 minutes, and neutralized with a saturated aqueous sodium bicarbonate solution. Chloroform layer is washed with water and dried over sodium sulfate, followed by distillation of the solvent. Recrystallization of the residue from acetone-n-hexane yields 8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepine as colorless flakes melting at 226°-227° C.

Workup

  1. stirringThe mixture is stirred at room temperature for further 30 minutes
  2. washChloroform layer is washed with water
  3. dry with materialdried over sodium sulfate
  4. distillationfollowed by distillation of the solvent
  5. customRecrystallization of the residue from acetone-n-hexane

Sources & evidence

ORD record
ord-20254a603c274d94a25071f88736f4d1
Source dataset
uspto-grants-1978_07
Patent number
US04102881

Linked notes

Loading…