3-chloro-N-(3-fluorophenyl)propanamide

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-fluoroaniline (20 g, 0.180 mol) in dichloromethane (100 mL) was added triethylamine (21.816 g, 0.216 mol) and 3-chloropropanoyl chloride (17.18 mL, 0.180 mol) under cooling condition (0° C.) with constant stirring. Reaction mass was allowed to stir at room temperature for 12 h. The reaction mixture was diluted with water (300 mL) and extracted with dichloromethane (4×100 mL). The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated under vacuum to obtain the title compound. 1H NMR (400 MHz, CDCl3) δ 7.51-7.48 (d, J=10.4 Hz, 1H), 7.42 (bs, 1H), 7.29-7.24 (dd, J=14.8 Hz, 8.0 Hz, 1H), 7.15-7.13 (d, J=8.0 Hz, 1H), 6.84-6.81 (t, J=6.8 Hz, 1H), 3.89-3.86 (t, J=6.4 Hz, 2H), 2.83-2.80 (t, J=6.4 Hz, 2H). MS (M+1): 201.9. Reaction mass extracted with dichloromethane (4×100 mL) The combined organic layer was washed with saturated aqueous sodium chloride solution dried over sodium sulphate concentrated under vacuum

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solid of 3-chloro-N-(3-fluorophenyl)propanamide (3 g, 14.88 mmol) was added AlCl3 (6.3 g, 0.047 mmol) and maintained with an inert atmosphere of nitrogen with stirring for 5 h at 120° C. The reaction was then quenched with ice-water, extracted with ethyl acetate (3×50 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography with 4% ethyl acetate in petroleum ether to afford 7-fluoro-1,2,3,4-tetrahydroquinolin-2-one as a white solid (1.5 g, 61%). maintained with an inert atmosphere of nitrogen The reaction was then quenched with ice-water extracted with ethyl acetate (3×50 ml) dried over anhydrous magnesium sulfate concentrated in vacuo The residue was purified by silica gel column chromatography with 4% ethyl acetate in petroleum ether

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-fluoroaniline (10 g, 90.00 mmol) in acetone (40 ml) was added pyridine (18 g, 227.56 mmol) and 3-chloropropanoyl chloride (13.73 g, 108.14 mmol) and the reaction was stirred for 3 h at 55° C. The resulting solution was extracted with ethyl acetate (3×50 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford 3-chloro-N-(3-fluorophenyl)propanamide as a yellow solid (13.21 g, 73%). The resulting solution was extracted with ethyl acetate (3×50 ml) dried over anhydrous magnesium sulfate concentrated in vacuo