Ethanol → Ethyl 4-chloropyridine-3-carboxylate

A suspension of 4-chloro-nicotinic acid (3.0 g, 19.0 mmol) in thionyl chloride (50 ml) was heated under reflux for 90 minutes. After cooling to ambient temperature, the solution was concentrated to dryness and then azeotroped with toluene (2×50 ml) to afford a solid. The resultant solid was added in portions to a cooled (0° C.) solution of ethanol (25 ml) and DIPEA (15 ml). The reaction was stirred at room temperature for 4 hours then concentrated in vacuo before water (75 ml) was added. The solution was extracted with ethyl acetate (2×75 ml) then the combined organic phases were dried over sodium sulfate then concentrated to give the title compound as a brown oil (3.3 g, 94%). 1H NMR (CDCl3, 400 MHz) 9.03 (s, 1H), 7.58 (d, J=5.4 Hz, 1H), 7.41 (dd, J=5.4 Hz, 0.5 Hz, 1H), 4.45 (q, J=7.3 Hz, 2H), 1.43 (t, J=7.3 Hz, 3H).

1. temperaturewas heated
2. temperatureunder reflux for 90 minutes
3. concentrationthe solution was concentrated to dryness
4. customazeotroped with toluene (2×50 ml)
5. customto afford a solid
6. additionThe resultant solid was added in portions to
7. concentrationthen concentrated in vacuo before water (75 ml)
8. additionwas added
9. extractionThe solution was extracted with ethyl acetate (2×75 ml)
10. dry with materialthe combined organic phases were dried over sodium sulfate
11. concentrationthen concentrated

ORD record

ord-a8218c44ba57485a9363e1847df3d7ad

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893085B2