Water → HCID 22047165, compound

Temperature

0 °C

Furo[2,3-c]pyridin-5-ylmethyl acetate (956 mg, 5 mmol) is dissolved in CH2Cl2 (40 mL) and cooled to 0° C. Chlorine gas is bubbled through the solution for 15 min, the cooling bath is immediately removed and the mixture stirred for 2 h. The mixture is re-cooled to 0° C., saturated with chlorine gas, the cooling bath removed and the solution warmed to rt. The solution is layered with saturated NaHCO3 (20 mL), stirred gently for 2 h then stirred vigorously for 15 min. The mixture is diluted with saturated NaHCO3 (50 mL), extracted with CH2Cl2 (1×40 mL then 1×20 mL), dried over K2CO3 and concentrated to a volume of 20 mL under a stream of nitrogen. The solution is diluted with EtOH (35 mL), treated with K2CO3 (4.09 g, 29.6 mmol) and stirred for 18 h at rt. Water (7 mL) is added and the mixture stirred for 2 days. The mixture is concentrated to dryness, partitioned between 50% saturated NaCl (50 mL) and CH2Cl2 (4×50 mL), dried over K2CO3 and concentrated in vacuo to a brown solid (833 mg). The crude material is chromatographed over a standard 40 g Biotage column, eluting with 50% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 624 mg (68%) of (3-chlorofuro[2,3-c]pyridin-5-yl)methanol as a yellow oil. 1H NMR (DMSO-d6): δ 4.69, 5.56, 7.69, 8.55, 8.93 ppm.

1. customChlorine gas is bubbled through the solution for 15 min
2. customthe cooling bath is immediately removed
3. temperatureThe mixture is re-cooled to 0° C., saturated with chlorine gas
4. customthe cooling bath removed
5. temperaturethe solution warmed to rt
6. stirringstirred gently for 2 h
7. stirringthen stirred vigorously for 15 min
8. additionThe mixture is diluted with saturated NaHCO3 (50 mL)
9. extractionextracted with CH2Cl2 (1×40 mL
10. dry with material1×20 mL), dried over K2CO3
11. concentrationconcentrated to a volume of 20 mL under a stream of nitrogen
12. additionThe solution is diluted with EtOH (35 mL)
13. stirringstirred for 18 h at rt
14. stirringthe mixture stirred for 2 days
15. concentrationThe mixture is concentrated to dryness
16. custompartitioned between 50% saturated NaCl (50 mL) and CH2Cl2 (4×50 mL)
17. dry with materialdried over K2CO3
18. concentrationconcentrated in vacuo to a brown solid (833 mg)
19. customThe crude material is chromatographed over a standard 40 g Biotage column
20. washeluting with 50% EtOAc/hexane
21. concentrationconcentrated

ORD record

ord-bcae1a1da0b145e6b45581abc98d4bdc

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06911543B2