3-Cyclopropyl-3-Oxopropionic Acid Methyl Ester → Methyl 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carboxylate

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12 g of methyl 3-cyclopropyl-3-oxopropionate and 25 g of 2-amino-4′-fluorobenzophenone methanesulfonate were added to 146 g of 2-propanol, and 2-propanol was distilled off at 79 to 83° C. After distilling off 119 g of 2-propanol over 6 hours, 1.14 g of methyl 3-cyclopropyl-3-oxopropionate was added and the mixture was heated at 79 to 81° C. for 4 hours. An analysis of the mixture with high performance liquid chromatography (HPLC) showed that the residual amount of 2-amino-4′-fluorobenzophenone as a raw material was 0.9%. 146 g of toluene was added into the reaction solution, and the reaction solution was washed with 80 g of 4% aqueous solution of sodium hydroxide and then 35 g of 2% aqueous solution of sodium hydroxide. The reaction solution was further washed with 25 g of 5% brine solution, and then dried over 5 g of anhydrous magnesium sulfate. Toluene was removed under a reduced pressure, and crystallization was carried out in 180 g of cyclohexane to obtain 22.9 g of methyl 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carboxylate.

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