A. Ethyl α-carbethoxy-β-m-chloroanilinoacrylate. A few boiling chips are added to a mixture of 127.5 g. (1.0 mole) of m-chloroaniline and 233 g. (1.1 moles) of ethyl ethoxymethylenemalonate （乙氧甲叉） in an open 500-ml. round-bottomed flask. The mixture is heated on a steam bath for 1 hour, the evolved ethanol being allowed to escape. The warm product is used directly in the next step.
B. 7-Chloro-4-hydroxy-3-quinolinecarboxylic acid. In a 5-l. round-bottomed flask equipped with an air condenser 1 l. of Dowtherm A is heated to vigorous boiling, and the product of the above step is poured in through the condenser. Heating is continued for 1 hour, during which time a large proportion of the cyclization product crystallizes. The mixture is cooled, filtered, and washed with two 400-ml. portions of Skellysolve B (b.p. 61–70°) to remove the major portion of colored impurities. The air-dried filter cake is mixed with 1 l. of 10% aqueous sodium hydroxide, and the mixture is refluxed vigorously until all the solid ester dissolves (about 1 hour). The saponification mixture is cooled, and the aqueous solution is separated from any oil that may be present. The solution is acidified to Congo red paper with concentrated hydrochloric acid (ca. 270 ml. of the 38% acid, sp. gr. 1.19) or 10% sulfuric acid. The 7-chloro-4-hydroxy-3-quinolinecarboxylic acid, weight 190–220 g. (85–98%), is collected by filtration and washed thoroughly with water. The dry acid melts at about 266° with effervescence.
C. 7-Chloro-4-quinolinol and 4,7-dichloroquinoline. The above air-dried acid is suspended in 1 l. of Dowtherm A in a 2-l. flask equipped with a stirrer and a reflux condenser. The mixture is boiled for 1 hour under a stream of nitrogen to assist in the removal of the water. The clear, light-brown solution is cooled to room temperature, and 90 ml. (150 g., 0.98 mole) of phosphorus oxychloride is added. The temperature is raised to 135–140°, and the mixture is stirred for 1 hour. The reaction mixture is cooled and poured into a separatory funnel. The portion of the mixture adhering to the flask is rinsed into the funnel with ether, and the solution is washed with three 500-ml. portions of 10% hydrochloric acid. The combined acid extracts are cooled in ice and neutralized with 10% sodium hydroxide to precipitate the 4,7-dichloroquinoline. The solid is collected, washed thoroughly with water, and dried; it weighs 130–145 g. (66–73%) and melts at 80–82°. The pure product is obtained by one recrystallization from Skellysolve B (b.p. 61–70°); weight 110–120 g. (55–60%), m.p. 84–85°.