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0 °C

To a cooled (-25° C.) solution of 2,3-O-isopropylidene-D-lyxono-1,4-lactone 3 (10.0 g, 53.2 mmol) and pyridine (8.38 g, 8.56 mL, 106.4 mmol) in CH2Cl2 (125 mL) was added dropwise via syringe triflic anhydride (16.5 g, 9.82 mL, 58.5 mmol) at a rate such that the reaction temperature did not exceed -18° C. After the addition was complete the reaction was gradually warmed to 0° C. over 1.5 h. TLC (silica, ethyl acetate/hexane:1/1) indicated no 3 remaining and the presence of a single new product (Rf= 0.45). The reaction mixture was poured into ice/water (250 mL), partitioned and the aqueous layer extracted with CH2Cl2 (2 x 50 mL). The organic layers were combined, washed with cold saturated aqueous CuSO4 (3×50 mL), water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated to provide a bright red-orange glassy solid (Rf, silica=0.12, tetrahydrofuran (THF)/hexane: 30/70) which still contained solvent. Crude triflate 5 was dissolved in N,N-dimethyformamide (DMF) (100 mL), cooled with an ice/water bath and sodium azide (6.92 g, 106.4 mmol) was slowly added. After the addition was complete, the cooling bath was removed and the mixture stirred at room temperature for 2.5 h. The DMF was removed by bulb-to-bulb distillation under vacuum (31° C. @0.7 mm Hg). The receiver bulb was cooled with a dry ice/acetone bath to increase the efficiency of the distillation. The resultant thick pasty residue was dissolved in CH2Cl2 (150 mL) and filtered to remove the inorganic salts. The filter cake was washed with CH2Cl2 (150 mL) and the combined filtrates were concentrated under vacuum. If desired, the resulting partially purified product can be used directly in the synthesis of compound 7. In this example, the residue was further purified by subjecting it to the above bulb-to-bulb distillation technique (for removal of the last traces of DMF) to provide 15.5 g of a crude red solid which was purified by flash chromatography [silica gel (100 g), ethyl acetate/hexane:1/1]to provide 10.09 g of 6 (89% yield) of a pale yellow solid: (Rf,silica=0.21, THF/hexane: 30/70), DISC mp 59.7° C.; Analysis Calculated for C8H11N3O4 : C, 45.07; H, 5.20; N, 19.71. Found: C, 44.98; H, 5.28; N, 19.28.

1. customdid not exceed -18° C
2. additionAfter the addition
3. custompartitioned
4. extractionthe aqueous layer extracted with CH2Cl2 (2 x 50 mL)
5. washwashed with cold saturated aqueous CuSO4 (3×50 mL), water (50 mL), brine (50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto provide a bright red-orange glassy solid (Rf, silica=0.12, tetrahydrofuran (THF)/hexane: 30/70) which still contained solvent
10. temperaturecooled with an ice/water bath
11. additionAfter the addition
12. customthe cooling bath was removed
13. customThe DMF was removed by bulb-to-bulb distillation under vacuum (31° C. @0.7 mm Hg)
14. temperatureThe receiver bulb was cooled with a dry ice/acetone bath
15. temperatureto increase
16. distillationthe efficiency of the distillation
17. dissolutionThe resultant thick pasty residue was dissolved in CH2Cl2 (150 mL)
18. filtrationfiltered
19. customto remove the inorganic salts
20. washThe filter cake was washed with CH2Cl2 (150 mL)
21. concentrationthe combined filtrates were concentrated under vacuum
22. customthe resulting partially purified product can be used directly in the synthesis of compound 7
23. distillationto the above bulb-to-bulb distillation technique (
24. customfor removal of the last traces of DMF)
25. customto provide 15.5 g of a crude red solid which
26. customwas purified by flash chromatography [silica gel (100 g), ethyl acetate/hexane