反应详情

A mixture of the above part (a) 1,3-dioxoisoindole (4.4 g., 0.01 mole), and 30 mesh granulated tin (2.8 g., 0.024 mole) in 20 ml of methanol and 12 ml. of concentrated hydrochloric acid was heated at 75°-80° for a 8 hr. period. Additional 1 g. portions of tin were added at the end of 5 hr. and 6 hr., respectively. After cooling, the reaction mixture was diluted with 40 ml. of methanol, heated to reflux and filtered through infusorial earth to remove unreacted tin. The filter-cake was washed with methanol and combined filtrates concentrated under reduced pressure. Residual oil slurried with warm methanol provided 1 g. of solid and cooling of the methanol decant an additional 2.1 g. of solid. The combined crude product was further purified by stirring with 65 ml. of 0.077N hydrochloric acid while slowly introducing a gaseous stream of hydrogen sulfide (H2S) during a 2.0 hr. period. Excess H2S was removed under reduced pressure, the mixture filtered through infursorial earth and the filter-cake extracted with warm methanol. Cooling the methanol filtrates provided 2.2 g. of product which crystallized from methanol-water gave analytically pure 6-chloro-2,3-dihydro-3-oxo-2-[1-(phenylmethyl)-4-piperidinyl]-1H-isoindole-5-sulfonamide hydrochloride as the monohydrate, m.p. 282°-284°.

1. custom6 hr
2. temperatureAfter cooling
3. additionthe reaction mixture was diluted with 40 ml
4. temperatureto reflux
5. filtrationfiltered through infusorial earth
6. customto remove unreacted tin
7. washThe filter-cake was washed with methanol and combined filtrates
8. concentrationconcentrated under reduced pressure
9. customprovided 1 g
10. customdecant an additional 2.1 g
11. customwas further purified
12. additionof 0.077N hydrochloric acid while slowly introducing a gaseous stream of hydrogen sulfide (H2S) during a 2.0 hr
13. customExcess H2S was removed under reduced pressure
14. filtrationthe mixture filtered through infursorial earth
15. extractionthe filter-cake extracted with warm methanol
16. temperatureCooling the methanol filtrates
17. customprovided 2.2 g
18. customof product which crystallized from methanol-water