Sodium Chloride → 2H-Isoindole-1-carboxylic acid, 5-chloro-2-(2-(diethylamino)ethyl)-3-phenyl-, ethyl ester, monohydrochloride

HRID 1973289Notes

Reaction equation

HRID 1973289 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:9]=2NC1=O)=[O:5])[CH3:2].[H-].[Na+].[ClH:27].[CH2:28]([N:30]([CH2:34][CH3:35])[CH2:31][CH2:32]Cl)[CH3:29].[Cl-].[Na+]>CN(C)C=O>[ClH:23].[CH2:1]([O:3][C:4]([C:6]1[N:12]([CH2:29][CH2:28][N:30]([CH2:34][CH3:35])[CH2:31][CH3:32])[C:11]([C:10]2[CH:9]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:13]2[C:18]=1[CH:17]=[CH:16][C:15]([Cl:27])=[CH:14]2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 133631-Chloro-2-(diethylamine)ethane hydrochlorideHCID 24758Sodium hydrideHCID 110682Ethyl 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylate

Product 1

HCID 30458932H-Isoindole-1-carboxylic acid, 5-chloro-2-(2-(diethylamino)ethyl)-3-phenyl-, ethyl ester, monohydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 27.2 g. of 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid ethyl ester in 480 ml. of dimethylformamide is treated under nitrogen at -10° C. with 0.33 mol. of sodium hydride (14.4 g. of a 55% dispersion in mineral oil) and stirred at the same temperature for 15 minutes. To this mixture, there are added at -10° C. to -5° C. 27.2 g. of 2-diethylaminoethyl chloride hydrochloride; the mixture is then stirred at room temperature for 1 hour and subsequently heated for 3 hours at 60° C. After cooling, the mixture is poured into 4 liters of ice-water with stirring; 200 g. of sodium chloride are added and the oily precipitate is separated be decantation. The latter is immediately dissolved in methylene chloride and the organic solution, shielded from daylight, is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and concentrated to dryness. The resulting oil is dissolved in 100 ml. of ether and filtered; the filtrate is treated with 180 ml. of 0.5-N hydrochloric acid and throughly shaken. After cooling in an ice-bath, the crystallized hydrochloride is removed by filtration, washed with water and ether and then dissolved in 200 ml. of methylene chloride. After separation of the aqueous layer, the methylene chloride solution is dried over sodium sulfate, filtered and treated portionwise with 150 ml. of ether, whereby there is obtained 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride; melting point 248°-250° C. (decomposition).

Workup

  1. additionTo this mixture, there are added at -10° C. to -5° C
  2. stirringthe mixture is then stirred at room temperature for 1 hour
  3. temperatureAfter cooling
  4. stirringwith stirring
  5. customthe oily precipitate is separated
  6. dissolutionThe latter is immediately dissolved in methylene chloride
  7. washis washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. dissolutionThe resulting oil is dissolved in 100 ml
  11. filtrationof ether and filtered
  12. additionthe filtrate is treated with 180 ml
  13. stirringof 0.5-N hydrochloric acid and throughly shaken
  14. temperatureAfter cooling in an ice-bath
  15. customthe crystallized hydrochloride is removed by filtration
  16. washwashed with water and ether
  17. dissolutiondissolved in 200 ml
  18. customAfter separation of the aqueous layer
  19. dry with materialthe methylene chloride solution is dried over sodium sulfate
  20. filtrationfiltered
  21. additiontreated portionwise with 150 ml

Sources & evidence

ORD record
ord-c5239f0c38474485a3e85046fb6457ae
Source dataset
uspto-grants-1976_12
Patent number
US03996374

Reaction notes

Loading…