3-chloro-N-(2-fluorophenyl)propanamide → 8-Fluoro-1,2,3,4-tetrahydroquinolin-2-one

Temperature

160 °C

3-Chloro-N-(2-fluorophenyl)propanamide (3.3 g, 16.4 mmol) and aluminum trichloride (10.9 g, 81.8 mmol) were combined in a RB flask with a stirbar and purged with argon. The mixture of the two solids was heated to 160° C. to form a melt, which was stirred for 1.5 h. The mixture was then removed from the heating bath and when it had cooled to below 100° C., was quenched by careful addition of water. The resulting mixture was cooled to room temperature, neutralized with NaOH, and extracted with dichloromethane (3×). The combined organics were dried, filtered and evaporated, then chromatographed on silica gel using 20% EtOAc in hexanes, giving the desired product. 1H NMR showed some impurities. Yield: 2.35 g, 88%. 1H NMR (CDCl3) δ 2.66 (t, 2H, J=7.6 Hz), 3.01 (t, 2H, J=7.6 Hz), 6.96 (m, 3H), 8.11 (brs, 1H).

1. custompurged with argon
2. additionThe mixture of the two solids
3. customto form a melt, which
4. customThe mixture was then removed from the heating bath and when it
5. temperaturehad cooled to below 100° C.
6. customwas quenched by careful addition of water
7. temperatureThe resulting mixture was cooled to room temperature
8. extractionextracted with dichloromethane (3×)
9. customThe combined organics were dried
10. filtrationfiltered
11. customevaporated
12. customchromatographed on silica gel using 20% EtOAc in hexanes

ORD record

ord-f3d96db2e1b9498ea9ce5978add121fa

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173813B2