反应详情

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 5 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 by 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 thoroughly 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).

1. additionTo this mixture, there are added at -10° C. to -5° C
2. temperaturesubsequently heated for 3 hours at 60° C
3. temperatureAfter cooling
4. stirringwith stirring
5. customthe oily precipitate is separated by decantation
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 thoroughly 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