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

HRID 1973284Notes

Reaction equation

HRID 1973284 reaction equation
[Na].Cl.[CH2:3]([N:5]([CH2:9][CH3:10])[CH2:6][CH2:7][Cl:8])[CH3:4].[CH2:11]([O:13][C:14]([C:16]1[NH:17][C:18]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:19]2[C:24]=1[CH:23]=[CH:22][C:21]([Cl:25])=[CH:20]2)=[O:15])[CH3:12].[Cl-].[Na+]>CN(C)C=O.C(O)C>[ClH:8].[CH2:11]([O:13][C:14]([C:16]1[N:17]([CH2:4][CH2:3][N:5]([CH2:9][CH3:10])[CH2:6][CH3:7])[C:18]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:19]2[C:24]=1[CH:23]=[CH:22][C:21]([Cl:25])=[CH:20]2)=[O:15])[CH3:12]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 133631-Chloro-2-(diethylamine)ethane hydrochlorideHCID 5360545Sodium2×HCID 54174784Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

Product 1

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

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Meanwhile, in a second flask, 4.6 g. of sodium are dissolved in 100 ml. of ethanol and treated at 0° C. with 34.5 g. of 2-diethylaminoethyl chloride hydrochloride. After dilution with 50 ml. of dimethylformamide and stirring for 30-40 minutes in an ice-bath, the obtained fine suspension is added dropwise at 0°-2° C. over a period of 15-20 minutes to the sodium derivative of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester prepared as in the foregoing paragraph. The mixture is subsequently stirred for 30 minutes at room temperature and then heated at 60° C. for 3 hours. After cooling, the mixture is poured into 4 liters of ice-water, 200 g. of sodium chloride are added and the separated oily product is immediately extracted with methylene chloride. The organic phase, 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 then taken up 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 crystallized hydrochloride is removed by filtration under suction, washed with water and ether and then dissolved in 700 ml. of methylene chloride. The aqueous layer is separated; the organic phase is dried over sodium sulfate, filtered and treated portionwise with 450 ml. of ether, whereby there is obtained 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride in the form of colorless crystals having a melting point of 248°-250° C. (decomposition). Crystallization from methylene chloride/ether does not increase the melting point.

Workup

  1. temperatureheated at 60° C. for 3 hours
  2. temperatureAfter cooling
  3. extractionthe separated oily product is immediately extracted with methylene chloride
  4. washis washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. additionof ether, treated with 280 ml
  8. stirringof 0.5-N hydrochloric acid and thoroughly shaken
  9. temperatureAfter cooling in an ice-bath
  10. customthe crystallized hydrochloride is removed by filtration under suction
  11. washwashed with water and ether
  12. dissolutiondissolved in 700 ml
  13. customThe aqueous layer is separated
  14. dry with materialthe organic phase is dried over sodium sulfate
  15. filtrationfiltered
  16. additiontreated portionwise with 450 ml

Sources & evidence

ORD record
ord-219a212cf07a459b9f12814f062d17f1
Source dataset
uspto-grants-1976_12
Patent number
US03996374

Reaction notes

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