Hydrochloric Acid → HCID 20226387, compound

Participants

Reaction Steps

45 g of 3-chloro-4-amino-benzoyl-propionic acid are stirred together with 50 ml of 35% formaldehyde solution and 440 ml of 0.5N sodium hydroxide solution for 17 hours at room temperature. The reaction mixture is adjusted with 2N hydrochloric acid to pH 5, and is extracted with ethyl acetate. The ethyl acetate phases are washed with water, dried over sodium sulfate and concentrated by evaporation. The residue, 3-(3-chloroamino-benzoyl)-3-hydroxymethyl)-propionic acid, is directly further reacted unpurified by being refluxed together with 1600 ml of ethanol and 18 ml of hydrazine hydrate for 5 hours. The reaction mixture is concentrated by evaporation, and the residue is distributed between 4N hydrochloric acid and ethyl acetate. The aqueous phases are rendered basic with a 2N sodium carbonate solution, and are extracted with ethyl acetate. The ethyl acetate extracts are washed twice with 2N sodium carbonate solution and with water, dried and then concentrated by evaporation. As residue is obtained the crude 6-(3-chloro-4-amino-phenyl)- 5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone, which together with 25 g of β,β-dibromodiethyl ether and 37 ml of diisopropylethylamine in 150 ml of dimethylformamide are refluxed for 18 hours. The reaction mixture is concentrated under high vacuum in a rotary evaporator; the residue is then taken up in ethyl acetate, and repeatedly washed with 1N hydrochloric acid and water. The organic phase is dried over sodium sulfate and concentrated by evaporation, the product which crystallises out being 6-(3-chloro-4-morpholino-phenyl)-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone, m.p. 172°-173° C.

Provenance & Evidence