CID 406 → Methyl 2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)acetate

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence