反应详情

A 1 L 3-neck flask was purged with nitrogen and charged with a solution of ethyl (6-aminopyridin-3-yl)acetate (31.7 g, 176 mmol) in EtOAc (317 mL) at +22° C. Then 30 mL of TMS trifluoroacetate was added (1.0 equiv) while cooling in a water bath. A mild exotherm to +25° C. and partial crystallization was observed. After 5 min, triethylorthoformate was added (44.0 mL, 264 mmol) followed by TMS-azide (28.0 mL, 211 mmol). The resulting suspension was stirred at +23° C. After 15 min, an additional 10 mL of TMS trifluoroacetate was added (0.30 equiv). A clear soln formed after ˜10 min. The mixture was stirred for 3 days at +20° C. whereupon a thin, light yellow suspension had formed. The mixture was cooled in an ice bath, and 200 mL of 1M aq K3PO4 was added while maintaining the temperature below +20° C. Then 465 mL EtOAc was added to solubilize the product. The layers were separated (pH of aq˜8), then the organic phase was washed with 2×250 mL water, and concentrated to a thick slurry. Then 400 mL of n-heptane was added to the concentrated organic phase over 20 min. After 30 rnM, the suspension was filtered to afford the title tetrazole product.

1. customA 1 L 3-neck flask was purged with nitrogen
2. temperaturewhile cooling in a water bath
3. customA mild exotherm to +25° C. and partial crystallization
4. additiontriethylorthoformate was added (44.0 mL, 264 mmol)
5. waitAfter 15 min
6. customA clear soln formed after ˜10 min
7. stirringThe mixture was stirred for 3 days at +20° C. whereupon a thin, light yellow suspension
8. customhad formed
9. temperatureThe mixture was cooled in an ice bath
10. temperaturewhile maintaining the temperature below +20° C
11. customThe layers were separated (pH of aq˜8)
12. washthe organic phase was washed with 2×250 mL water
13. concentrationconcentrated to a thick slurry
14. additionThen 400 mL of n-heptane was added to the concentrated organic phase over 20 min
15. filtrationAfter 30 rnM, the suspension was filtered