Hexachloroethane → 2-Chloro-7-methoxyfuro[2,3-c]pyridine

Temperature

-15 °C

A 0.13 M solution of 7-methoxyfuro[2,3-c]pyridine (250 mg, 1.7 mmol) in THF stirred at −78° C. under an atmosphere of nitrogen was treated with n-BuLi (1.6M in hexanes, 450 uL, 5.2 mmol) dropwise over 30 sec. The mixture was warmed gradually to −15° C. over a period of 7 to 10 min. After 1 h at −15° C., the mixture was cooled to −65° C. and was treated with a 0.26 M solution of hexachloroethane (473 mg, 2 mmol) in THF by dropwise addition over 3 min. After stirring at −65° C. for 15 min, the mixture was allowed to gradually warm to rt. After the mixture was allowed to stir overnight, it was quenched with water (5 mL) and extracted with EtOAc (3×15 ml). The combined organic layers were washed brine (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using a gradient of EtOAc (5 to 30%) in hexanes to afford the title compound (266 mg, 87%) as an amber oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.99-4.08 (m, 3H) 7.13 (s, 1H) 7.25 (d, J=5.31 Hz, 1H) 7.95 (d, J=5.31 Hz, 1H). LCMS (M+H)+=184.

1. temperaturethe mixture was cooled to −65° C.
2. temperatureto gradually warm to rt
3. stirringto stir overnight
4. customit was quenched with water (5 mL)
5. extractionextracted with EtOAc (3×15 ml)
6. washThe combined organic layers were washed brine (10 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-213c7b5eefda467b81bf74ee32a5c146

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115114B2