Synthetic Route of 62257-15-2, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 62257-15-2 as follows.
Example 9: Intermediate 9~ 8-fluoro-5-methoxy-2-methylquinoline[0235] 8-Fluoro-5-methoxy-2-methylquinoline was synthesized from 2-fluoro-5-methoxyaniline (30.0 g, 213 mmol) according to the procedures described above for 8-chloro-5-methoxy-2- methylquinoline hydrochloride (Intermediate 1 , Step 1) with the following change: The hydrochloride salt was dissolved in dichloromethane (400 mL) and the pH of the resulting solution was adjusted to 8-9 with saturated aqueous potassium carbonate solution. The resulting mixture was extracted with dichloromethane, and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 20% ethyl acetate-petroleum ether) to afford 8-fluoro-5- methoxy-2-methylquinoline (25.2 g, 62%) as a yellow solid. MS (ESI, pos. ion) m/z 192[M+H]+. Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride [0204] A 1000-mL 3-necked round-bottom flask was charged with 2-chloro-5-methoxy aniline (50 g, 317 mmol), -butanol (120 mL), concentrated hydrochloric acid (37%, 90 mL), and chloranil (tetrachloro-l ,4-benzoquinone) (78 g, 317 mmol). The resulting solution stirred for 1 h at 100 C in an oil bath. A solution of (E)-crotonaldehyde (28.9 mL, 349 mmol) in -butanol (50 mL) was added dropwise over 1 h. The resulting solution stirred for 1 h at 100 C in an oil bath and was then cooled to 70 C. Tetrahydrofuran (650 mL) was added, and the reaction mixture stirred for 1 h at 70 C and was then cooled to 0 C. The resulting precipitate was held at 0- 5 C for 1 h. The mixture was filtered, the solids were washed with cold (ca. 0 C) THF (2 x 350 mL), and then dried in an oven to afford 8-chloro-5-methoxy-2-methylquinoline hydrochloride (83.0 g, 74%) as a yellow solid. MS (ES, m/z): 208 [M+H]+
According to the analysis of related databases, 62257-15-2, the application of this compound in the production field has become more and more popular.
Reference:
Patent; BAIR, Kenneth W.; HERBERTZ, Torsten; KAUFFMAN, Goss Stryker; KAYSER-BRICKER, Katherine J.; LUKE, George P.; MARTIN, Matthew W.; MILLAN, David S.; SCHILLER, Shawn E. R.; TALBOT, Adam C.; WO2015/74064; (2015); A2;,
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