Nordiazepam → 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-1-acetic acid methyl ester

HRID 1580601Notes

Reaction equation

HRID 1580601 reaction equation
C[O-].[Na+].[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:14][C:13](=[O:15])[CH2:12][N:11]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]=2[CH:22]=1.CN(C)C=O.Br[CH2:29][C:30]([O:32][CH3:33])=[O:31]>C1(C)C=CC=CC=1>[CH3:33][O:32][C:30](=[O:31])[CH2:29][N:14]1[C:8]2[CH:7]=[CH:6][C:5]([Cl:4])=[CH:22][C:9]=2[C:10]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:11][CH2:12][C:13]1=[O:15]

Participants

6

Reactant 4

HCID 2997NordiazepamHCID 6228DimethylformamideHCID 60984Methyl bromoacetateHCID 10942334Sodium Methoxide

Product 1

HCID 149939577-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-1-acetic acid methyl esterYield 42%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Sodium methoxide (5.95 g., 0.11 mole) is added to a solution of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (27 g., 0.1 mole) in 200 ml. of dimethylformamide and the mixture is stirred and heated on a steambath for about 20 minutes. To this mixture is added a solution of methyl bromoacetate (16.7 g., 0.11 mole) in 165 ml. of toluene during 1 hour while stirring and heating are continued. The mixture is heated for an additional 2 hours, allowed to stand overnight at room temperature (about 25° C.) and evaporated to dryness in vacuo. The residue is stirred with 500 ml. of water until a suspension results. The suspension is filtered and the solid thus obtained is crystallized first from ether and then from ethanol to give 14.5 g. (42% yield) of 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-1-acetic acid methyl ester of melting point 137°-138° C.

Workup

  1. temperatureheated on a steambath for about 20 minutes
  2. temperatureheating
  3. temperatureThe mixture is heated for an additional 2 hours
  4. custom(about 25° C.) and evaporated to dryness in vacuo
  5. customof water until a suspension results
  6. filtrationThe suspension is filtered
  7. customthe solid thus obtained
  8. customis crystallized first from ether
  9. customfrom ethanol to give 14.5 g

Sources & evidence

ORD record
ord-15b7373a0a03435ea7bdf0bfc05c4c20
Source dataset
uspto-grants-1976_01
Patent number
US03933816

Reaction notes

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