Water → HCID 70606826, compound

HRID 1863093Notes

Reaction equation

HRID 1863093 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]([CH:12]2[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:16]3[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:15]=3N(C)C2=O)=[O:11])[CH2:3][CH2:2]1.CN(C)C=O.[H-].[Na+].O>C(#N)C>[ClH:29].[O:1]1[CH2:2][CH2:3][N:4]([CH2:7][CH2:8][O:9][C:10]([C:12]2[NH:18][C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:16]3[C:15]=2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25]3)=[O:11])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 53728414HCID 53728414, compound

Product 1

HCID 70606826HCID 70606826, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 19.7 g. of 7-chloro-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid 2-morpholinoethyl ester in 200 ml. of dimethylformamide is treated under an atmosphere of argon at 0° C. with 0.10 mol of sodium hydride (4.4 g. of a 55% dispersion in mineral oil) and the mixture is stirred at room temperature for 30 minutes. The mixture is then warmed to 100° C. over a period of about 30 minutes and then stirred at this temperature for 1 hour. After cooling, 12 ml. of water are added dropwise and the mixture is poured on to 600 ml. of ice-water. After the addition of 30 g. of sodium chloride, the separated product is extracted with methylene chloride. The organic phase is washed with water, dried over sodium sulfate and concentrated to dryness. For purification, the solid residue obtained is boiled for about 10 minutes in 50 ml. of acetonitrile and then cooled in an ice-bath. The crude base is removed by filtration, taken up in methylene chloride and treated with excess ethereal hydrochloric acid. After the addition of diethyl ether, there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid 2-morpholinoethyl ester hydrochloride in the form of greenish crystals which melt at 240°-242° C. (decomposition). Recrystallization from methanol/diethyl ether does not increase the melting point.

Workup

  1. temperatureThe mixture is then warmed to 100° C. over a period of about 30 minutes
  2. stirringstirred at this temperature for 1 hour
  3. temperatureAfter cooling
  4. additionthe mixture is poured on to 600 ml
  5. additionAfter the addition of 30 g
  6. extractionof sodium chloride, the separated product is extracted with methylene chloride
  7. washThe organic phase is washed with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. customFor purification
  11. customthe solid residue obtained
  12. waitis boiled for about 10 minutes in 50 ml
  13. customThe crude base is removed by filtration
  14. additiontreated with excess ethereal hydrochloric acid
  15. additionAfter the addition of diethyl ether

Sources & evidence

ORD record
ord-1bd2f1c7ba314f89bcc630949c8123f3
Source dataset
uspto-grants-1979_09
Patent number
US04167632

Reaction notes

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