Ammonia → Nordiazepam

HRID 1973069Notes

Reaction equation

HRID 1973069 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=O)=[O:4].[NH3:21]>>[Cl:20][C:17]1[CH:18]=[CH:19][C:6]2[NH:5][C:3](=[O:4])[CH2:2][N:21]=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:7]=2[CH:16]=1

Participants

3

Reactant 2

HCID 222Ammonia2×HCID 776355-Chloro-2-(chloroacetamido)benzophenone

Product 1

HCID 2997NordiazepamYield 81.4%

Procedure

A mixture of paraformaldehyde (147.2 g.) and methanol (550 ml.) was stirred and heated to reflux with a steady stream of ammonia bubbling in. The crystal slurry of hexamethylenetetramine which formed was cooled to room temperature and 2-chloroacetamido-5-chlorobenzophenone (308.2 g., 1.0 mol) was added in one portion. With ammonia bubbling in, the reaction mixture was heated at reflux for 10 hours. The flow of ammonia was interrupted and the reaction mixture was cooled to room temperature, filtered, washed with methanol (2 × 125 ml.) and hot water (4 × 500 ml) and dried. There was obtained 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (220.4 g., 81.4%) melting at 212.5° to 215° C.

Workup

  1. temperatureat reflux for 10 hours
  2. temperaturethe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. washwashed with methanol (2 × 125 ml.) and hot water (4 × 500 ml)
  5. customdried

Sources & evidence

ORD record
ord-4462c7337bba49bd942d6a552c0b148b
Source dataset
uspto-grants-1976_12
Patent number
US03996209

Reaction notes

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