Ammonia → Uxepam

HRID 442331Notes

Reaction equation

HRID 442331 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=2[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH:5][CH2:4][C:3]1=[O:20].[C:21](=[O:24])(O)[O-].[Na+].C(Cl)(Cl)=O.[NH3:30]>C1C=CC=CC=1.CO>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=2[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:5]([C:21](=[O:24])[NH2:30])[CH2:4][C:3]1=[O:20]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 30819844,5-Dihydrodiazepam

Product 1

HCID 68787UxepamYield 87.5%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 887MethanolSolvent

Procedure

2.1 g. (7.32 mmoles) of (+)-1-methyl-5-phenyl-7-chloro-1,3,4,5-tetrahydro-2H-1,4-benzodiazepine-2one are dissolved in 20 ml. of benzene. 1.26 g. of solid sodium bicarbonate are added to the solution, and then 22 ml. of a 10% solution of phosgene in benzene are added dropwise at 10° to 15° C. The mixture is stirred for 2 hours, then 10 ml. of a 10% solution of ammonia in methanol are added, and the mixture is stirred at room temperature overnight. The separated inorganic salts are filtered off, and the filter cake is washed with benzene. The filtrate is evaporated to dryness under reduced pressure, and the residue is recrystallized from ethanol. 2.12 g. (87.5 %) of (-)-1-methyl-4-carbamoyl-5-phenyl-7-chloro-1,3,4,5-tetrahydro-2H-1,4-benzodiazepine-2-one are obtained; m.p.: 214°-217° C., [α]D25 = -616.5° (c = 1, chloroform).

Workup

  1. stirringthe mixture is stirred at room temperature overnight
  2. filtrationThe separated inorganic salts are filtered off
  3. washthe filter cake is washed with benzene
  4. customThe filtrate is evaporated to dryness under reduced pressure
  5. customthe residue is recrystallized from ethanol

Sources & evidence

ORD record
ord-88a39bf36c4c40468e09224860122ba7
Source dataset
uspto-grants-1977_08
Patent number
US04045433

Reaction notes

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