Diazepam → Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

HRID 1112498Notes

Reaction equation

HRID 1112498 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2N(C)C(=O)[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.[H-].[Na+].C(O[C:26](=[O:30])[O:27][CH2:28][CH3:29])C.[Cl-].[Na+]>CN(C)C=O>[CH2:28]([O:27][C:26]([C:9]1[NH:8][C:7]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:6]2[C:5]=1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:20]2)=[O:30])[CH3:29]

Participants

6

Reactant 4

HCID 3016DiazepamHCID 5234Sodium ChlorideHCID 7766Diethyl CarbonateHCID 24758Sodium hydride

Product 1

HCID 54174784Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 28.5 g. of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one in 400 ml. of dimethylformamide is treated under an atmosphere of argon at -10° C. with 0.25 mol. of sodium hydride (11.0 g. of a 55% dispersion in mineral oil) and the mixture is stirred at the same temperature for 15 minutes. The suspension is then treated at -10° C. to -5° C. with a solution of 35.5 g. of diethylcarbonate in 50 ml. of dimethylformamide. The mixture is stirred at 20° C. for 1 hour and at 60° C. for an additional 4 hours. Then, the mixture is poured on to a mixture of 100 g. of sodium chloride and 2.5 kg. of ice. The precipitate is removed by filtration, washed with water and dissolved in methylene chloride. The organic solution is washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to dryness. The crystalline residue is heated to reflux with 500 ml. of ethanol for 10 minutes and then cooled in an ice-bath. After filtration and washing with ethanol and diethyl ether, there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in the form of greenish crystals having a melting point of 208°-210° C. (decomposition). Recrystallization from acetonitrile does not increase the melting point.

Workup

  1. additionThe suspension is then treated at -10° C. to -5° C. with a solution of 35.5 g
  2. stirringThe mixture is stirred at 20° C. for 1 hour and at 60° C. for an additional 4 hours
  3. additionThen, the mixture is poured on to a mixture of 100 g
  4. customThe precipitate is removed by filtration
  5. washwashed with water
  6. dissolutiondissolved in methylene chloride
  7. washThe organic solution is washed with a saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. temperatureThe crystalline residue is heated
  11. temperatureto reflux with 500 ml
  12. waitof ethanol for 10 minutes
  13. temperaturecooled in an ice-bath
  14. filtrationAfter filtration
  15. washwashing with ethanol and diethyl ether

Sources & evidence

ORD record
ord-7101eeabbe22476b877cf6766edf4ccb
Source dataset
uspto-grants-1978_10
Patent number
US04122265

Reaction notes

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