Picolinic acid → HCID 410739, compound

Temperature

0 °C

A slurry of picolinic acid (10.2 g, 83.3 mmol) in 100 mL of thionyl chloride was stirred at ambient temperature for 10 min. Dimethylformamide (0.5 mL) was carefully added dropwise via a syringe. After 3 hours the mixture became a clear, homogeneous solution. Excess thionyl chloride and dimethylformamide were removed under reduced pressure. The residue was azeotroped 3× with dry toluene, dissolved in 100 mL of dichloromethane, cooled to 0° C. and treated dropwise with diethylamine (34.5 mL, 330 mmol) over a 12 minute period. The reaction mixture was stirred for 72 hours at ambient temperature and then filtered through a pad of Celite® filter aid. The filtrate was poured into 200 mL of water. The organic phase was collected and the aqueous phase was extracted with 3×100 mL of dichloromethane. The combined organic extracts were washed successively with 1N NaOH, water, and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by normal phase flash chromatography eluting with 100% ethyl acetate. Like fractions containing product were combined and concentrated under reduced pressure to give N,N diethylpicolinamide 14. (12.6 g, 70.8 mmol). 1H NMR (400 MHz, Chloroform-d) δ 8.47 (ddd, J=4.8, 1.7, 1.0 Hz, 1H), 7.71-7.62 (m, 1H), 7.45 (ddd, J=7.8, 1.9, 0.8 Hz, 1H), 7.27-7.17 (m, 1H), 3.46 (q, J=7.1 Hz, 2H), 3.26 (q, J=7.1 Hz, 2H), 1.16 (t, J=7.1 Hz, 3H), 1.04 (t, J=7.1 Hz, 3H). LCMS: (M+H)+, 179.

1. customExcess thionyl chloride and dimethylformamide were removed under reduced pressure
2. customThe residue was azeotroped 3× with dry toluene
3. dissolutiondissolved in 100 mL of dichloromethane
4. filtrationfiltered through a pad of Celite®
5. filtrationfilter aid
6. additionThe filtrate was poured into 200 mL of water
7. customThe organic phase was collected
8. extractionthe aqueous phase was extracted with 3×100 mL of dichloromethane
9. washThe combined organic extracts were washed successively with 1N NaOH, water, and brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe crude material was purified by normal phase flash chromatography
14. washeluting with 100% ethyl acetate
15. additionLike fractions containing product
16. concentrationconcentrated under reduced pressure

ORD record

ord-11662aee4d2d446591f5f7eddff36cb6

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394299B2