Ethanol → Ethyl 2-chloro-6-methoxyisonicotinate

Temperature

0 °C

To a previously sonicated suspension of 2-chloro-6-methoxyisonicotinic acid (4.0 g, 21 mmol) in ethanol (50 mL) was added thionyl chloride (4.64 mL, 64.0 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 2 h and then at room temperature for 18 h. Thionyl chloride (4.64 mL, 64.0 mmol) was slowly added and the mixture was stirred at room temperature for 4 h. The reaction mixture was quenched by slowly pouring into a saturated aqueous solution of sodium bicarbonate (200 mL). Ice was added to the mixture to lower the temperature. The mixture was extracted with diethyl ether (150 mL×2). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford a clear syrup as crude product. The crude product was dried for 2 h under high vacuum while heating to 80° C. The resulting residue was concentrated from toluene (500 mL) to afford ethyl 2-chloro-6-methoxyisonicotinate as an off white solid (3.205 g). 1H NMR (400 MHz, CDCl3) δ 1.40 (s, 3H), 3.98 (s, 3H), 4.39 (s, 2H), 7.22 (s, 1H), 7.44 (s, 1H).

1. waitat room temperature for 18 h
2. stirringthe mixture was stirred at room temperature for 4 h
3. customThe reaction mixture was quenched
4. additionby slowly pouring into a saturated aqueous solution of sodium bicarbonate (200 mL)
5. additionIce was added to the mixture
6. extractionThe mixture was extracted with diethyl ether (150 mL×2)
7. washThe combined organics were washed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto afford a clear syrup as crude product
12. dry with materialThe crude product was dried for 2 h under high vacuum
13. temperaturewhile heating to 80° C
14. concentrationThe resulting residue was concentrated from toluene (500 mL)

ORD record

ord-76278c8f0c41429c8ea52a16272c6567

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2