反应详情

温度

0 °C

To a 0° C. solution of diethyl 1,3-dithian-2-ylphosphonate (12.0 g, 46.8 mmol, prepared as described in Saito, T. et al., J. Am. Chem. Soc. 1998 120 (45) 11633-11644) in THF (300 mL) was added n-BuLi (20.0 mL, 49.9 mmol, 2.5 M in hexanes) dropwise. The mixture was stirred at 0° C. for 10 minutes and was cooled to −78° C. A solution of 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine-6-carbaldehyde (5.15 g, 31.2 mmol) in THF (50 mL) was added dropwise via a cannula to the phosphonate solution. The mixture was slowly warmed to room temperature over 4 hours. Saturated NH4Cl was added and the aqueous solution was washed with EtOAc. The organic solution was dried (Na2SO4) and concentrated in vacuo to provide the crude ketene dithioacetal. To a solution of the crude ketene in MeOH (400 mL) was added silver nitrate (17.2 g, 101 mmol). The reaction was heated to 60° C. overnight. The reaction was cooled to room temperature and was filtered through Celite®. The filter cake was washed with EtOAc and the filtrate was concentrated to afford methyl 2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)acetate (5.50 g) which was used without further purification in the next step.

1. temperaturewas cooled to −78° C
2. temperatureThe mixture was slowly warmed to room temperature over 4 hours
3. washthe aqueous solution was washed with EtOAc
4. dry with materialThe organic solution was dried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customto provide the crude ketene dithioacetal
7. temperatureThe reaction was heated to 60° C. overnight
8. temperatureThe reaction was cooled to room temperature
9. filtrationwas filtered through Celite®
10. washThe filter cake was washed with EtOAc
11. concentrationthe filtrate was concentrated