Ethanol → Ethyl 3-chloroisonicotinate

A suspension of 3-chloro-isonicotinic acid (1.0 g, 6.35 mmol) in thionyl chloride (10 ml) was heated under reflux for 2.5 hours. After cooling to ambient temperature, the solution was concentrated to dryness and then azeotroped with toluene (10 ml) to afford an oil. The resultant oil was added dropwise over 10 minutes to a cooled (0° C.) solution of ethanol (15 ml) and DIPEA (5 ml). The reaction was stirred at room temperature for 18 hours then concentrated in vacuo before water (20 ml) was added. The solution was extracted with ethyl acetate (30 ml) and the organic phase was dried over sodium sulfate then concentrated to give the title compound as an orange oil (1.1 g, 94%). 1H NMR (CDCl3, 400 MHz) 8.72 (s, 1H), 8.59 (d, J=4.9 Hz, 1H), 7.63 (dd, J=4.9 Hz, 0.5 Hz, 1H), 4.44 (q, J=7.3 Hz, 2H), 1.42 (t, J=7.3 Hz, 3H).

1. temperaturewas heated
2. temperatureunder reflux for 2.5 hours
3. concentrationthe solution was concentrated to dryness
4. customazeotroped with toluene (10 ml)
5. customto afford an oil
6. additionThe resultant oil was added dropwise over 10 minutes to
7. concentrationthen concentrated in vacuo before water (20 ml)
8. additionwas added
9. extractionThe solution was extracted with ethyl acetate (30 ml)
10. dry with materialthe organic phase was dried over sodium sulfate
11. concentrationthen concentrated

ORD record

ord-ade761b03d8e4a80a9374a6546de2073

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893085B2