Chloroacetyl chloride → 6-(2-Chloroacetyl)-1,2,3,4-tetrahydroquinolin-2-one

Participants

Reaction Conditions

Reaction Steps

To a 10 L, 4-neck flask, fitted with a mechanical stirrer and under N2, AlCl3 (408 g, 3.06 mol) and dry CH2Cl2 (2.7 L, 18 vol) was added. Chloroacetylchloride (89 mL, 1.22 mol) was then added from an addition funnel gradually over 15 minutes at room temperature. The resulting mostly clear solution was maintained at that temp for 30 minutes and turned into a muddy mixture. A solution of 3,4-dihydroquinolin-2(1H)-one (150 g, 1.02 mol) and CH2Cl2 (0.3 L, 2 vol) was added, over 1.5 hours, at such a rate as to keep the internal temperature below 30° C. The resulting brown mixture was stirred at that temp for 2 hours, then heated at 40° C. for an additional 2 hours, and then left to stir overnight at room temperature. The reaction mixture was cooled in an ice bath and connected to an HCl gas trap. Ice-cold H2O (total 3 L) was then added, over 1.5 hours, at such a rate as to keep the internal temperature below 30° C. The resulting mixture was stirred at room temperature for 1 hour and then heated at 40-50° C. to remove the CH2Cl2. To this mixture, THF (1 L) was added and the mixture was stirred at room temperature overnight. The solids were collected by filtration. The yellow cake was washed with H2O (500 mL), THF (200 mL) and hexane (1 L×2) and it was dried in a vacuum oven (@50° C., 1 day) to afford 6-(2-chloroacetyl)-3,4-dihydroquinolin-2(1H)-one (221 g, 97%). 1H NMR (270 MHz, d-DMSO) δ 10.48 (s, 1 H), 7.86-7.77 (m, 2 H), 6.96 (d, J=8.2 Hz, 1 H), 5.08 (s, 2 H), 2.96 (t, J=7.6 Hz, 2 H), 2.51 (t, J=7.6 Hz, 2 H)

Provenance & Evidence