Hydrochloric Acid → (2,4-Dimethoxy-benzylamino)-acetic acid

Participants

Reaction Steps

N-(2,4-Dimethoxybenzyl)glycine is prepared by reacting glycine with 2,4-dimethoxybenzaldehyde in the presence of sodium hydroxide, reducing with palladium-on-carbon in methanol and subsequently neutralizing with 2N hydrochloric acid. The aqueous solution obtained is concentrated. 18.6 g of the mixture of N-(2,4-dimethoxybenzyl)glycine and sodium chloride obtained are stirred at 80° and 90°, in each case for 1 hour, together with 60 ml of N,N-dimethylformamide and 10 g (50.6 mmol) of 6-chloroisatoic anhydride. The reaction mixture is evaporated and the residue is heated at 135°-140° for 5 hours in a high vacuum. The crystalline product is boiled in 90 ml of N,N-dimethylformamide, whereupon the mixture is poured into 400 ml of hot water. The mixture is left to cool to room temperature while stirring, then cooled to about 0° in an ice-bath, the product is filtered off under suction, rinsed with water and the material obtained is dissolved in 20 ml of hot N,N-dimethylformamide. After the addition of 150 ml of ethyl acetate the mixture is left to stand in an ice-bath for 1 hour, the product is filtered off under suction, rinsed with cold ethyl acetate and dried at 80° in vacuo. There is obtained 6-chloro-4-(2,4-dimethoxybenzyl)-3,4-dihydro-2H-1,4-benzodiazepine-2,5(1H)-dione of melting point 230°-231°.

Provenance & Evidence