反应详情

温度

0 °C

Trimethylaluminium (2.384 mL, 4.77 mmol) was added to pyridin-2-amine (0.390 g, 4.15 mmol) in toluene (30 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (1.2 g, 4.15 mmol) in toluene (10 mL) was added and the reaction was allowed to warm to room temperature and then heated at 80° C. for 4 hours. The reaction mixture was cooled, 20% Rochelle salt in water (75 mL) added and stirred for 2 hours. The mixture was extracted with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (50 mL) and brine (50 mL), dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc to afford the product (1.25 g).

1. temperatureto warm to room temperature
2. temperatureheated at 80° C. for 4 hours
3. temperatureThe reaction mixture was cooled
4. stirringstirred for 2 hours
5. extractionThe mixture was extracted with ethyl acetate (2×5 mL)
6. washthe combined organic extracts washed with water (50 mL) and brine (50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated
10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc