p-Toluenesulfonic acid → Alprazolam

HRID 1764515Notes

Reaction equation

HRID 1764515 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.[C:21]([O-])([O-])(OCC)[CH3:22].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:21]([CH3:22])=[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

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 123908747-Chloro-2-hydrazinyl-5-phenyl-3H-1,4-benzodiazepineHCID 86598186Ethyl ortho-acetate

Product 1

HCID 2118Alprazolam

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 2.84 parts of 7-chloro-2-hydrazino-5-phenyl-3-H-1,4-benzodiazepine in 50 parts by volume of chloroform are added 10 parts of ethyl orthoacetate and 4 parts of p-toluenesulfonic acid. The solution is left standing at room temperature for 6 hours and heated for a while on a water-bath to complete the reaction. The mixture is washed with saturated aqueous sodium bicarbonate, then with water and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is treated in a similar manner to Example 18 to give 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-a][1,4] benzodiazepine as colorless needles. Melting point: 224° C to 225° C.

Workup

  1. waitThe solution is left
  2. temperatureheated for a while on a water-bath
  3. customthe reaction
  4. washThe mixture is washed with saturated aqueous sodium bicarbonate
  5. dry with materialwith water and dried over anhydrous sodium sulfate
  6. customAfter evaporation of the solvent
  7. additionthe residue is treated in a similar manner to Example 18

Sources & evidence

ORD record
ord-c041eba224cd4f41b2679d1a219c7aac
Source dataset
uspto-grants-1978_09
Patent number
US04116956

Reaction notes

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