Hydrochloric Acid → HCID 118075721, compound

Temperature

100 °C

A mixture of 5-cyclobutoxy-2,3-difluorobenzenamine hydrogen chloride (9.9 g, 42.1 mmol), concentrated hydrochloric acid (36 mL), chloranil (12.32 g, 49.8 mmol) in n-butanol (60 mL) stirred for 1 h at 100° C. (E)-Crotonaldehyde (19.8 mL, 239 mmol) was added dropwise, and the resulting solution stirred for 1 h at 100° C. and was then cooled to 70° C. Tetrahydrofuran (600 mL) was added, and the mixture stirred for another 30 min at 70° C. The reaction mixture was cooled to room temperature and concentrated under vacuum. The residue was poured into water (300 mL) and the pH of the mixture was adjusted to 7-8 with saturated aqueous potassium carbonate solution. The resulting mixture was extracted with ethyl acetate (3×300 mL), 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 25% ethyl acetate/petroleum ether) to afford 5-cyclobutoxy-7,8-difluoro-2-methylquinoline hydrochloride (6 g, 57%) as a yellow solid. MS (ESI, pos. ion) m/z 250 [M+H]+.

1. additionwas added dropwise
2. temperaturewas then cooled to 70° C
3. stirringthe mixture stirred for another 30 min at 70° C
4. temperatureThe reaction mixture was cooled to room temperature
5. concentrationconcentrated under vacuum
6. additionThe residue was poured into water (300 mL)
7. extractionThe resulting mixture was extracted with ethyl acetate (3×300 mL)
8. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customThe residue was purified via column chromatography on silica gel (eluting with 25% ethyl acetate/petroleum ether)

ORD record

ord-9e879a1b76b34cacaedded58c4785e37

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388161B2