Benzyl Bromide → HCID 59316606, compound

To a solution of 6-(2,4-difluorophenyl)-3,4-dihydroquinolin-2(1H)-one (130 mg, 0.50 mmol) in anhydrous tetrahydrofuran (5 mL) at 0° C. in a dry flask equipped with an inlet of dry nitrogen was added fresh 1.6 M n-butyl lithium in n-hexane (0.6 mL, 0.96 mmol) with stirring. The reaction mixture was stirred at 0° C. for 2 hours, followed by addition of a second portion of 1.6 M n-butyl lithium in n-hexane (0.6 mL, 0.96 mmol), and the mixture stirred for another 2 hours. To this mixture was added slowly a solution of benzyl bromide (855 mg, 5.00 mmol) in anhydrous tetrahydrofuran (3 mL) at 0° C., stirred overnight, and allowed to warm to room temperature. The reaction was followed by LCMS and stirring was continued until all of the starting material was consumed. The reaction mixture was quenched by slow addition of saturated aqueous ammonium chloride (10 mL) with stirring, concentrated under reduced pressure, diluted with ethyl acetate (20 mL) and dilute aqueous ammonium chloride (10 mL). The aqueous phase was extracted with ethyl acetate (3×20 mL), and the combined organic phase successively washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL), and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a crude mixture, which was purified by reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 1-benzyl-6-(2,4-difluorophenyl)-3,4-dihydroquinolin-2(1H)-one (62 mg, 0.18 mmol, 35%). LCMS mz 350.0 (M+H), 372.0 (M+Na), anal HPLC>98% in purity. 1H NMR (400 MHz; CDCl3) δ7.10-7.40 (m, 8H); 6.80-7.00 (m, 3H); 5.22 (s, 2H); 3.05 (m, 2H); 2.85 (m, 2H).

1. stirringThe reaction mixture was stirred at 0° C. for 2 hours
2. stirringthe mixture stirred for another 2 hours
3. stirringstirred overnight
4. stirringstirring
5. customwas consumed
6. customThe reaction mixture was quenched by slow addition of saturated aqueous ammonium chloride (10 mL)
7. stirringwith stirring
8. concentrationconcentrated under reduced pressure
9. additiondiluted with ethyl acetate (20 mL) and dilute aqueous ammonium chloride (10 mL)
10. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
11. washthe combined organic phase successively washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL)
12. dry with materialdried over magnesium sulfate
13. customEvaporation of the solvent under reduced pressure
14. customgave a crude mixture, which
15. customwas purified by reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%)

ORD record

ord-61b9ee9731f345dfac4dee88872ce358

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664379B2