1-Chloro-2-(diethylamine)ethane hydrochloride → 2-[2-(Diethylamino)ethyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride

HRID 372301Notes

Reaction equation

HRID 372301 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][CH:11]=[CH:10]2)=[O:5])[CH3:2].[H-].[Na+].Cl.[CH2:24]([N:26]([CH2:30][CH3:31])[CH2:27][CH2:28][Cl:29])[CH3:25]>CN(C)C=O>[ClH:29].[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:25][CH2:24][N:26]([CH2:30][CH3:31])[CH2:27][CH3:28])[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][CH:11]=[CH:10]2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 133631-Chloro-2-(diethylamine)ethane hydrochlorideHCID 24758Sodium hydrideHCID 53760678Ethyl 3-phenyl-2H-isoindole-1-carboxylate

Product 1

HCID 706205782-[2-(Diethylamino)ethyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 26.5 g. of 3-phenylisoindole-1-carboxylic acid ethyl ester in 600 ml. of dimethylformamide is treated under nitrogen at -10° C. with 0.40 mol. of sodium hydride (17.5 g. of a 55% dispersion in mineral oil) and stirred at the same temperature for 15 minutes. Then, at -10° C. to -5° C. there are added 34.5 g. of 2-diethylaminoethyl chloride hydrochloride. The mixture is stirred for 1 hour at room temperature and subsequently heated for 3 hours at 60° C. The mixture is cooled and poured into 8 liters of ice-water. After the addition of 300 g. of sodium chloride, the oily precipitate is separated by decantation and immediately dissolved in methylene chloride. The 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 200 ml. of ether, treated with 280 ml. of 0.5 -N hydrochloric acid and thoroughly shaken. After cooling in an ice-bath, the separated hydrochloride is removed by filtration under suction, washed with water and ether and then dissolved in methylene chloride. The aqueous layer is separated and the methylene chloride solution is dried over sodium sulfate and filtered. After the addition of ether, there is obtained 2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride; melting point 230°-232° C. (decomposition).

Workup

  1. additionThen, at -10° C. to -5° C. there are added 34.5 g
  2. stirringThe mixture is stirred for 1 hour at room temperature
  3. temperatureThe mixture is cooled
  4. additionAfter the addition of 300 g
  5. customof sodium chloride, the oily precipitate is separated by decantation
  6. dissolutionimmediately 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 200 ml
  11. additionof ether, treated with 280 ml
  12. stirringof 0.5 -N hydrochloric acid and thoroughly shaken
  13. temperatureAfter cooling in an ice-bath
  14. customthe separated hydrochloride is removed by filtration under suction
  15. washwashed with water and ether
  16. dissolutiondissolved in methylene chloride
  17. customThe aqueous layer is separated
  18. dry with materialthe methylene chloride solution is dried over sodium sulfate
  19. filtrationfiltered
  20. additionAfter the addition of ether

Sources & evidence

ORD record
ord-f02e0ee226f44750bf3276847e1bbe13
Source dataset
uspto-grants-1978_05
Patent number
US04090027

Reaction notes

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