反应详情

A sample of the crude product from Step A (approximately 89%, 56.0 g, 0.18 mole) was dissolved in acetonitrile (400 mL) and a solution of NaH2PO4 (120 g, 0.87 mole) in 520 mL of water was added. Sodium hypochlorite solution (5.25% in water, 128 g, 2.6 mole) was added dropwise over 10–15 minutes. The orange solution was maintained at room temperature for 30 minutes. The reaction mixture was cooled in an ice bath and a solution of NaClO2 in 560 mL of water was added dropwise, keeping the temperature below 11° C. Gas evolution was observed and an aqueous sodium hydroxide scrubber was used to quench evolved chlorine. After the addition was complete, the reaction mixture was kept cold for one hour then allowed to reach room temperature overnight. To the reaction mixture was added 80 mL of concentrated hydrochloric acid dropwise to bring the pH below 3. The reaction mixture was extracted twice with ethyl acetate and the combined organic extracts were added dropwise rapidly with stirring to a cooled (<15° C.) solution of 300 g of NAHSO3 in 1300 mL of water. The mixture was partitioned and the aqueous phase extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was taken up in chlorobutane and reconcentrated (twice). The resulting brown solid was titurated in 100 mL of ethyl ether in hexane (1%). Small portions of chlorobutane were added to help granulate the solid. The product was collected via filtration, washed with hexanes and dried. The product consisted of 40.8 g of tan solid, which was essentially pure based upon 1H NMR.

1. temperatureThe reaction mixture was cooled in an ice bath
2. customthe temperature below 11° C
3. customto quench
4. additionAfter the addition
5. waitto reach room temperature overnight
6. additionTo the reaction mixture was added 80 mL of concentrated hydrochloric acid dropwise
7. extractionThe reaction mixture was extracted twice with ethyl acetate
8. additionthe combined organic extracts were added dropwise rapidly
9. temperaturea cooled (<15° C.) solution of 300 g of NAHSO3 in 1300 mL of water
10. customThe mixture was partitioned
11. extractionthe aqueous phase extracted with ethyl acetate
12. washThe combined organic phases were washed with saturated brine
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. additionSmall portions of chlorobutane were added
17. filtrationThe product was collected via filtration
18. washwashed with hexanes
19. customdried