Water → HCID 59316618, compound

Temperature

86 °C

To a solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (1a) (226 mg, 1.00 mmol) and 3-fluorophenylboronic acid (210 mg, 1.50 mmol) in N,N-dimethylformamide (10 mL) was added potassium carbonate (415 mg, 3.00 mmol) and water (2.0 mL). The reaction mixture was stirred for 5 minutes under an atmosphere of dry N2, and PdCl2(PPh3)2 (35 mg, 0.05 mmol) was added. The resulting mixture was heated at 86° C. for 5 hours, cooled, diluted with ethyl acetate (20 mL), filtered through a layer of celite which was washed with ethyl acetate (60 mL), the filtrate transferred to a separation funnel, and washed with 2 N potassium carbonate (20 mL), followed by 30% ammonium chloride (40 mL), then brine (50 mL). The solvent was removed from the organic layer under rescued pressure, to provide a pale yellow solid. To this crude product was added methanol (2 mL), the mixture sonicated, filtered, washed with cold methanol (3.0 mL), and dried under reduced pressure, to afford 6-(3-fluorophenyl)-3,4-dihydroquinolin-2(1H)-one, the compound of Formula (I) in which R1 is hydrogen, as a white solid; MS mz 242.1 (M+H), anal HPLC>97% in purity. 1H NMR (400 MHz; dmso-D6) δ 10.21 (s, 1H); 7.58 (d, J=2.1 Hz, 1H); 7.42-7.55 (m, 4H); 7.15 (m, 1H); 6.96 (d, J=8.2 Hz, 1H); 3.42 (t, J=7.6 Hz, 2H); 2.97 (t, J=7.6 Hz, 2H).

1. temperaturecooled
2. filtrationfiltered through a layer of celite which
3. washwas washed with ethyl acetate (60 mL)
4. customthe filtrate transferred to a separation funnel
5. washwashed with 2 N potassium carbonate (20 mL)
6. customThe solvent was removed from the organic layer under rescued pressure
7. customto provide a pale yellow solid
8. customthe mixture sonicated
9. filtrationfiltered
10. washwashed with cold methanol (3.0 mL)
11. customdried under reduced pressure

ORD record

ord-34eefc46e6444658a4f470831eb131f2

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664379B2