Dimethylformamide → Ethyl 2,5-dichloronicotinate

5-Chloro-2-hydroxynicotinic acid [11.95 g; Synthetic Comm. (1989), 19, 553] was suspended in thionyl chloride (52 mL) and anhydrous dimethylformamide (2 mL) was added. The suspension was refluxed 3 h, then concentrated under a nitrogen stream to remove the bulk of excess thionyl chloride before adding anhydrous ethanol (30 mL) giving a mixture of the desired ester and diethyl sulfite. The resulting mixture was concentrated in vacuo to remove the ethanol yielding a suspension. The solids were then filtered off and washed with anhydrous diethyl ether (2×10 mL). The combined filtrates were concentrated in vacuo yielding crude product. Purification by silica gel chromatography (ethyl acetate:hexanes 8:92) gave pure title compound (4.75 g).

1. temperatureThe suspension was refluxed 3 h
2. concentrationconcentrated under a nitrogen
3. customto remove the bulk of excess thionyl chloride
4. additionbefore adding anhydrous ethanol (30 mL)
5. customgiving
6. concentrationThe resulting mixture was concentrated in vacuo
7. customto remove the ethanol yielding a suspension
8. filtrationThe solids were then filtered off
9. washwashed with anhydrous diethyl ether (2×10 mL)
10. concentrationThe combined filtrates were concentrated in vacuo
11. customyielding crude product
12. customPurification by silica gel chromatography (ethyl acetate:hexanes 8:92)

ORD record

ord-85c227ba86c94703860bb2d9efdc8202

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07250518B2