反应详情

A solution of Example 3B (19.7 g, 77.1 mmol) and sodium bisulfite (8.0 g, 77.1 mmol) in water (500 mL) at 5° C. was stirred for 24 hours, warmed to room temperature, treated with a solution of potassium cyanide (5.1 g, 78.8 mmol) in ethyl acetate (350 mL), and stirred for 5 hours. The aqueous phase was separated and extracted with ethyl acetate. The combined extracts were washed sequentially with water and brine, dried (MgSO4), filtered, and concentrated. The concentrate was dissolved in dioxane (150 mL), treated with 12M HCl (150 mL), heated to reflux, stirred for 21 hours, and cooled to room temperature. The mixture was concentrated, dissolved in a mixture of water (30 mL) and acetone (200 mL), adjusted to pH 5.5 with 1M NaOH, treated with acetone (3.5 L), and cooled to 0° C. for 4 hours. The resulting precipitate was collected by filtration. The filter cake was dried, dissolved in 1:1 water/dioxane, treated with BOC-ON (1.2 eq.), and triethylamine (2 eq.), heated to 45° C., stirred for 15 hours, treated with 10% aqueous KHSO4, and extracted with ethyl acetate. The extract was washed sequentially with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product.

1. customThe aqueous phase was separated
2. extractionextracted with ethyl acetate
3. washThe combined extracts were washed sequentially with water and brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe concentrate was dissolved in dioxane (150 mL)
8. additiontreated with 12M HCl (150 mL)
9. temperatureheated
10. temperatureto reflux
11. stirringstirred for 21 hours
12. temperaturecooled to room temperature
13. concentrationThe mixture was concentrated
14. dissolutiondissolved in a mixture of water (30 mL) and acetone (200 mL)
15. additiontreated with acetone (3.5 L)
16. temperaturecooled to 0° C. for 4 hours
17. filtrationThe resulting precipitate was collected by filtration
18. customThe filter cake was dried
19. dissolutiondissolved in 1:1 water/dioxane
20. temperatureheated to 45° C.
21. stirringstirred for 15 hours
22. extractionextracted with ethyl acetate
23. washThe extract was washed sequentially with water and brine
24. dry with materialdried (MgSO4)
25. filtrationfiltered
26. concentrationconcentrated