Hydrochloric Acid → 2-Chloro-5-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazole

Participants

Reaction Conditions

Reaction Steps

To a mixture of 5-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazol-2-amine (4.0 mmol) from Step 1 and copper (0.04 g, 0.62 mmol) in hydrochloric acid (37%, 6 mL) and acetic acid (30 mL) at 0° C. was slowly added sodium nitrite (2.8 g, 40 mmol) while maintaining an internal reaction temperature below 10° C. After 1 h stirring at 0° C., the resulting mixture was stirred with gradual warming to ambient temperature over 2 h. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and evaporated in vacuo. Flash chromatography on a Biotage® purification apparatus (silica gel, 10 to 60% ethyl acetate in hexanes) yielded the title compound (0.66 g, 0.86 mmol, 22%) as yellow oil.

Provenance & Evidence