Dimethyl Sulfoxide → 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde

Temperature

2.5 °C

(3,4-Dihydro-2H-pyrano[2,3-c]pyridin-6-yl)methanol (300 g, 1.0 eq), DCM (1.5 L) and dimethyl sulfoxide (216 mL, 2.05 eq) were added with stirring to a vessel maintained at ˜0 to 5° C. Triethylamine (858 mL, 4.1 eq) followed by solid pyridine sulphur trioxide (474 g, 2.0 eq) were slowly added to the mixture while maintaining the mixture temperature at ˜0 to 7° C. The mixture was stirred at ˜0 to 7° C. for ˜5 to 8 h then quenched with aqueous 5 wt % NaHCO3 solution (3 L) to form a biphasic mixture. The layers were separated and the aqueous layer was extracted with DCM (0.9 L). The combined organic layers were washed with aqueous 5 wt % citric acid (3.0 L) and brine (300 mL), dried over anhydrous sodium sulfate and filtered to provide the title compound in DCM solution. 1H NMR (300 MHz, CDCl3) δ ppm 9.94 (s, 1H), 8.21-8.32 (m, 1H), 7.72 (s, 1H), 4.25-4.40 (m, 2H), 2.85 (t, J=6.50 Hz, 2H), 1.97-2.19 (m, 2H).

1. additionwere slowly added to the mixture
2. temperaturewhile maintaining the mixture temperature at ˜0 to 7° C
3. stirringThe mixture was stirred at ˜0 to 7° C. for ˜5 to 8 h
4. customthen quenched with aqueous 5 wt % NaHCO3 solution (3 L)
5. customto form a biphasic mixture
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with DCM (0.9 L)
8. washThe combined organic layers were washed with aqueous 5 wt % citric acid (3.0 L) and brine (300 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered

ORD record

ord-6f848ea9f4df491595c1bf199fc4ec5f

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759523B2