Picolinic acid → HCID 410739, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence