反应详情

A solution of n-butyllithium in hexanes (2.5 M, 22.5 mL, 56.3 mmol) was added dropwise by syringe to a stirring solution of 1-methyl-1H-1,2,3-triazole (5.00 g, 60.2 mmol, prepared according to PCT Int. Appl., 2008098104) in dry tetrahydrofuran (400 mL) at −55° C. The resulting off-white slurry was stirred at −45° C. for 20 minutes, whereupon a solution of 2,6-dimethyl-pyridine-3-carbaldehyde (8.33 g, 61.7 mmol) in dry tetrahydrofuran (10 mL) was added dropwise by syringe. After 5 minutes, the cooling bath was removed and the reaction mixture was allowed to slowly warm. After 45 minutes, saturated aqueous ammonium chloride solution (10 mL) and ethyl acetate (100 mL) were added. The mixture was concentrated by rotary evaporation. The residue was dissolved in ethyl acetate (300 mL). The organic solution was washed with saturated aqueous sodium chloride solution (100 mL, containing excess solid sodium chloride). The aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were combined and the combined solution was concentrated. Ether (100 mL) was added to the residue and the mixture was sonicated for 20 minutes during which time a white solid crashed out. The solids were collected by filtration. Ether (100 mL) was added to the collected solids and the mixture sonicated a second time. After 20 minutes, the mixture was filtered and the solids were collected to provide the title compound as a fine powder.

1. additionwas added dropwise by syringe
2. customthe cooling bath was removed
3. temperatureto slowly warm
4. waitAfter 45 minutes
5. additionsaturated aqueous ammonium chloride solution (10 mL) and ethyl acetate (100 mL) were added
6. concentrationThe mixture was concentrated by rotary evaporation
7. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
8. washThe organic solution was washed with saturated aqueous sodium chloride solution (100 mL, containing excess solid sodium chloride)
9. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
10. concentrationthe combined solution was concentrated
11. additionEther (100 mL) was added to the residue
12. customthe mixture was sonicated for 20 minutes during which time a white solid
13. filtrationThe solids were collected by filtration
14. additionEther (100 mL) was added to the collected solids
15. customthe mixture sonicated a second time
16. waitAfter 20 minutes
17. filtrationthe mixture was filtered
18. customthe solids were collected