反应详情

A solution of 25.0 g (0.145 mole) of 2-(4-chlorophenoxy)ethanol (Lancaster Synthesis Inc., Windham, N.H. 03087) in 64.6 g (0.640 mole) of triethylamine and 40 ml of methylene chloride was added in a thin stream to a solution of 83.3 g (0.580 mole) of dimethylsulfamoyl chloride (Aldrich) in 60 ml of methylene chloride stirred at ambient temperature in a water bath. The reaction mixture was stirred for 8 days at ambient temperature. The solids were removed by filtration and the filtrate was evaporated under reduced pressure to yield a viscous residue. The residue was partitioned between water and ethyl ether (300 ml each). The organic layer was washed with two 200 ml portions of 2N hydrochloric acid. Once with 200 ml of water, dried over magnesium sulfate and the solvent evaporated under reduced pressure to yield a viscous residue. The residue was treated with 65.0 g (0.63 mole) of triethylamine and the reaction mixture was stirred for 5 days at ambient temperature. The solids were removed by filtration and the filtrate was evaporated under reduced pressure and the viscous residue was partitioned between water and ethyl ether (450 ml each). The organic layer was washed with four 300 ml portions of water (pH neutral to pH paper), dried over magnesium sulfate and the solvent evaporated under reduced pressure to yield a brown viscous oily residue. The oil was purified by chromatography (4.5×90 cm glass column; 500 g of silica gel; methylene chloride). Fractions containing the title compound were combined and the solvent evaporated under reduced pressure to yield a viscous oil. The oil was dissolved in 150 ml of isopropyl ether and filtered to remove some insolubles. The filtrate was concentrated to a viscous oil. The oil was triturated with isopropyl ether-petroleum ether (bp range 30°-60° C.), cooled (refrigerator) and the resulting solid was collected by filtration. The solid was recrystallized from isopropyl ether to give 18.5 g (45%) of white solid, mp 54°-57° C.

1. stirringThe reaction mixture was stirred for 8 days at ambient temperature
2. customThe solids were removed by filtration
3. customthe filtrate was evaporated under reduced pressure
4. customto yield a viscous residue
5. customThe residue was partitioned between water and ethyl ether (300 ml each)
6. washThe organic layer was washed with two 200 ml portions of 2N hydrochloric acid
7. dry with materialOnce with 200 ml of water, dried over magnesium sulfate
8. customthe solvent evaporated under reduced pressure
9. customto yield a viscous residue
10. stirringthe reaction mixture was stirred for 5 days at ambient temperature
11. customThe solids were removed by filtration
12. customthe filtrate was evaporated under reduced pressure
13. customthe viscous residue was partitioned between water and ethyl ether (450 ml each)
14. washThe organic layer was washed with four 300 ml portions of water (pH neutral to pH paper)
15. dry with materialdried over magnesium sulfate
16. customthe solvent evaporated under reduced pressure
17. customto yield a brown viscous oily residue
18. customThe oil was purified by chromatography (4.5×90 cm glass column; 500 g of silica gel; methylene chloride)
19. additionFractions containing the title compound
20. customthe solvent evaporated under reduced pressure
21. customto yield a viscous oil
22. filtrationfiltered
23. customto remove some insolubles
24. concentrationThe filtrate was concentrated to a viscous oil
25. customThe oil was triturated with isopropyl ether-petroleum ether (bp range 30°-60° C.)
26. temperaturecooled (refrigerator)
27. filtrationthe resulting solid was collected by filtration
28. customThe solid was recrystallized from isopropyl ether