反应详情

温度

60 °C

Trimethylbromosilane (122 g.) was added dropwise to a solution of diethyl 3-(N-ethoxycarbonyl-N-ethoxycarbonyloxyamino)-2-(tetrahydro-2H-pyran-2-yloxy)propylphosphonate (79.4 g.) in methylene chloride (160 ml.) under ice-cooling with stirring over a period of 15 minutes. The mixture was further stirred for an hour at 0°-5° C. and for additional 2.5 hours at ambient temperature, and then evaporated under reduced pressure. The oily residue was dissolved in water (500 ml.) stirred at ambient temperature for an hour, and then washed twice with chloroform (200 and 100 ml. portions) to remove off bis(trimethylsilyl)ether. The combined chloroform washings were back extracted once with water (50 ml.). The combined aqueous layers were evaporated under reduced pressure. The dark brown oily residue was dissolved in water (300 ml.) washed twice with chloroform (each 150 ml. portion) and ethyl acetate (100 ml.) successively, treated with activated charcoal (2.5 g.), and evaporated under reduced pressure. The oily residue was dissolved in 1 N hydrochloric acid (750 ml.) treated with activated charcoal (2.5 g.) and then heated to reflux for 13.5 hours. The mixture was evaporated under reduced pressure. The oily residue was dissolved in a mixture of water (50 ml.) and methanol (100 ml.) adjusted to pH about 4 with propylene oxide, and diluted with ethanol (300 ml.). The oily precipitates were collected by decantation, and dissolved in water (60 ml.). This aqueous solution was diluted with methanol (120 ml.) under heating at 60° C., and then allowed to stand overnight at ambient temperature. The precipitates were collected by filtration, washed twice with 80% aqueous methanol (each 20 ml. portion) and methanol (20 ml.), and then dried on phosphorus pentoxide to give 2-hydroxy-3-(N-hydroxyamino)-propylphosphonic acid (10.60 g.). M.p. 153°-155° C.

1. temperaturecooling
2. stirringThe mixture was further stirred for an hour at 0°-5° C. and for additional 2.5 hours at ambient temperature
3. customevaporated under reduced pressure
4. dissolutionThe oily residue was dissolved in water (500 ml.)
5. stirringstirred at ambient temperature for an hour
6. washwashed twice with chloroform (200 and 100 ml. portions)
7. customto remove off bis(trimethylsilyl)ether
8. extractionThe combined chloroform washings were back extracted once with water (50 ml.)
9. customThe combined aqueous layers were evaporated under reduced pressure
10. dissolutionThe dark brown oily residue was dissolved in water (300 ml.)
11. washwashed twice with chloroform (each 150 ml
12. additionportion) and ethyl acetate (100 ml.) successively, treated with activated charcoal (2.5 g.)
13. customevaporated under reduced pressure
14. dissolutionThe oily residue was dissolved in 1 N hydrochloric acid (750 ml.)
15. additiontreated with activated charcoal (2.5 g.)
16. temperatureheated
17. temperatureto reflux for 13.5 hours
18. customThe mixture was evaporated under reduced pressure
19. dissolutionThe oily residue was dissolved in a mixture of water (50 ml.) and methanol (100 ml.)
20. additiondiluted with ethanol (300 ml.)
21. customThe oily precipitates
22. customwere collected by decantation
23. dissolutiondissolved in water (60 ml.)
24. additionThis aqueous solution was diluted with methanol (120 ml.)
25. waitto stand overnight at ambient temperature
26. filtrationThe precipitates were collected by filtration
27. washwashed twice with 80% aqueous methanol (each 20 ml
28. dry with materialportion) and methanol (20 ml.), and then dried on phosphorus pentoxide