1. Synthesis of 2-chloro-N-[2-(diethylamino)ethyl]-4-quinoline carboxamide
At room temperature, 200 g of 2-hydroxy-4-quinoline carboxylic acid and 1500 ml of toluene were added dropwise to a 3000 ml three-necked flask with stirring. The mixture was heated to 75 °C and reacted for 2 hours. The temperature was lowered to 25 °C and concentrated under reduced pressure. Then, 500 ml of toluene was added and the mixture was concentrated to dryness under reduced pressure. The solution was diluted directly with 2000 ml of toluene and added to a 5000 ml three-necked flask. 100 g of N,N-diethyldiethylamine was added. The mixture was heated to 70 °C and stirred until the reaction was complete. The temperature was lowered to room temperature, water was added and stirred for 30 minutes. The mixture was separated into liquid and liquid layers. The organic layer was washed twice with water and once with saturated brine. The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to obtain 274 g of 2-chloro-N-[2-(diethylamino)ethyl]-4-quinoline carboxamide, i.e., octocamide, with a yield of 85%.
2. Synthesis of Cincocaine 200g of cincoamide, 550ml of n-butanol, and 300g of sodium n-butoxide were added to a 3000ml reaction flask. The mixture was gradually heated to reflux for 3 hours, then cooled to room temperature. 1000ml of purified water was added, and the mixture was stirred for 30 minutes. After standing for 30 minutes to separate the layers, the aqueous layer was discarded. The organic layer was dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. Then, 500ml of toluene was added, and the mixture was heated to 60℃ and stirred for 30 minutes. After standing, the layers separated. The upper toluene layer was cooled to crystallize, yielding 146g of purified Cinchocaine, with a yield of 65% and a purity of 99.7%.
