Hydrochloric Acid → 8-Chloro-5-methoxy-2-methylquinoline hydrochloride

Temperature

100 °C

A 1000-mL 3-necked round-bottom flask was charged with 2-chloro-5-methoxyaniline (50 g, 317 mmol), n-butanol (120 mL), concentrated hydrochloric acid (37%, 90 mL), and chloranil (tetrachloro-1,4-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 n-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 (2×350 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]+

1. stirringThe resulting solution stirred for 1 h at 100° C. in an oil bath
2. temperaturewas then cooled to 70° C
3. stirringthe reaction mixture stirred for 1 h at 70° C.
4. temperaturewas then cooled to 0° C
5. waitThe resulting precipitate was held at 0-5° C. for 1 h
6. filtrationThe mixture was filtered
7. washthe solids were washed with cold (ca. 0° C.) THF (2×350 mL)
8. customdried in an oven

ORD record

ord-7876ff8af06b4157888e63d67341a69a

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388161B2