2-Chloro-N-ethyl-nicotinamide synthesis

Yield:52943-22-3 98.03 %

Reaction Conditions:

with triethylamine hydrochloride in toluene at 75;

Steps:

4 Example 4 N-ethyl-2-chloronicotinamide

The catalyst is loaded with 10% tin chloride, 1% zinc, and the rest is silicon dioxide powder. Add the above raw materials in an appropriate amount of methanol solvent according to the formula ratio, stir at about 30°C for 48h, slowly increase the temperature, evaporate the solvent methanol to dryness, and activate at 500°C to obtain solid catalyst;Weigh 47.4g (0.5mol) of 3-chloroacrolein with a purity of 95%, 68.6g (0.60mol) of 2-cyano-N-ethyl-acetamide with a purity of 98%, and 189.5g of toluene, and dissolve them in the reaction flask. Add 5.6g of triethylamine hydrochloride, raise the temperature to 75°C, keep the temperature for 4 hours, then take a sample to detect 0.42% of 3-chloroacrolein by HPLC, and end the reaction; lower the temperature to 40°C, add 6g of composite catalyst, and stir at this temperature for 2 hours , Gradient heating and heat preservation, every 10°C increase, heat preservation 0.5h, to 80°C heat preservation 0.5h, sampling ultra-high performance liquid phase detection intermediate I residual 0.09%, the end of heat preservation; filter while hot to recover the catalyst, add activated carbon at about 50°C for decolorization After 0.5h, the solvent was evaporated to dryness after filtration, and the N-ethyl-2-chloronicotinamide target product was obtained 92.0g, with a content of 98.3%, and a yield of 98.03%.

References:

CN115260092,2022,A Location in patent:Paragraph 0046-0049