Diethyl (ethoxymethylene)malonate → Diethyl (aminomethylidene)propanedioate

Temperature

190 °C

A mixture of 2-chloro-5-trifluoromethylaniline (3.91 g) and diethyl ethoxymethylenemalonate (4.0 mL) is heated at 190° C. for 2 h and is then diluted with diphenyl ether (30 mL). The mixture is allowed to cool to rt, filtered, and the white solid is washed with hexane (2×10 mL) to afford 1.632 g of the diethyl amino-methylenemalonate. The resulting intermediate (2.63 g) is suspended in diphenyl ether (30 mL) and heated to reflux with a Dean-Stark trap for 3 h. The mixture is allowed to cool to rft and is then poured into hexane (50 mL). The solid is filtered and then washed with hexane (20 mL) and hexane/diethyl ether (1/1, 20 mL) to afford 1.273 g of the quinolinecarboxylate ethyl ester. Te he ester (4 00 mg) and 4-chlorobenzylamine (1.52 mL) are heated at 190° C. for 1 h. The resulting mixture is diluted with toluene (4 mL), allowed to cool to rt, and then poured into hexane (50 mL). The solvent is decanted and the remaining oil is crystallized (acetic acid, water) to afford 285 mg of the title compound as a brown solid.

1. temperatureto cool to rt
2. filtrationfiltered
3. washthe white solid is washed with hexane (2×10 mL)

ORD record

ord-5b8c68eec34448c3af58b0ab3ac313b4

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06093732