Hydrochloric Acid → HCID 18663598, compound

Participants

Reaction Steps

10.82 g (44.40 mmol) of (2-chloro-6-phenoxy-phenyl)-acetonitrile and 7.85 g (53.72 mmol) of oxalic acid diethyl ester are added at room temperature to a freshly prepared sodium ethanolate solution (1.5 g (53.72 mmol) of sodium in 50 ml of ethanol) and the mixture is stirred for 18 hours. The mixture is rendered acidic with 1N hydrochloric acid, concentrated using a rotary evaporator and extracted 2× with ethyl acetate, and the organic phase is washed with brine, dried over sodium sulfate and concentrated to yield 15.99 g of crude intermediate (3-(2-chloro-6-phenoxy-phenyl)-2-hydroxy-4-nitrilo-but-2-enoic acid ethyl ester) 15.0 g (approximately 43.6 mmol) of the above intermediate are placed in 105 ml of glacial acetic acid and stirred for 20 minutes, 51.9 ml of water and 51.9 ml of sulfuric acid are slowly added, and the mixture is heated for 4 hours under reflux and then for 18 hours at room temperature. The reaction mixture is extracted with ethyl acetate, the organic phase is washed with water and 3× with 4N sodium hydroxide, and the aqueous phase is extracted 1× with ethyl acetate. The aqueous phases are rendered acidic with concentrated hydrochloric acid and extracted 3× with ethyl acetate, and the organic phase is dried over sodium sulfate and concentrated. 7.71 g (28.27 mmol)=60.3% of 1-chloro-dibenz[b,f]oxepine-10-carboxylic acid are obtained in the form of a yellow solid; TLC (silica gel; ethyl acetate/hexane=1:1; UV): Rf =0.21; 1H-NMR (CDCl3, 200 MHz): 7.15-7.47 (m, 7H); 7.68 (m, 1H), 8.39 (s, 1H).

Provenance & Evidence