Ethyl 2-methylacetoacetate → HCID 178432198, compound

Participants

Reaction Conditions

Reaction Steps

A mixture composed of 2.2 g of 3-chloro-4-(4-chlorophenoxy)-aniline, 2.63 g of ethyl 2-methylacetoacetate, and 0.5 mL of ethanol was added dropwise to 3.8 g of polyphosphoric acid heated to 150° C. The mixed solution was stirred at 150 to 160° C. while removing ethanol by evaporation for 3 hr. The reaction solution was poured into 175 mL of iced water containing 2 mL of concentrated hydrochloric acid to produce crystals. The crystals were collected by filtration and were recrystallized from water/methanol to give 2.8 g of a mixture of 5-chloro-6-(4-chlorophenoxy)-4-hydroxy-2,3-dimethyl-quinoline with 7-chloro-6-(4-chlorophenoxy)-4-hydroxy-2,3-dimethyl-quinoline (yield 93%). The mixture (2.8 g) was stirred in 42 mL of acetic anhydride with heating at 120 to 125° C. for one hr. The reaction solution was concentrated, ethyl acetate was then added to the concentrate, the mixture was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and the solvent was removed under the reduced pressure to give a crude product. The crude product was purified by column chromatography on silica gel (BW300, manufactured by Fuji Sylysia Chemical Ltd., solvent: n-hexane/ethyl acetate) to give 1.03 g of 4-acetoxy-5-chloro-6-(4-chlorophenoxy)-2,3-dimethyl-quinoline (yield 32.6%) and 0.68 g of 4-acetoxy-7-chloro-6-(4-chlorophenoxy)-2,3-dimethyl-quinoline (yield 21.0%).

Provenance & Evidence