Pyridine → HCID 14217296, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence