Potassium Carbonate → HCID 21291594, compound

Participants

Reaction Conditions

Reaction Steps

While stirring at 0° C., 2.7 g (19 mmol) of α-chloroethylchloroformate (cf. J. Org. Chem. 49, 2081 (1984)) are added dropwise to a solution of 4.7 g (12.7 mmol) of 4-chloro-5-cyano-N-(2-benzylethylaminoethyl)-2-methoxybenzamide (cf. Example 2) and 90 mg (0.6 mmol) of potassium carbonate in 200 ml of dichloroethane. The whole is then heated under reflux for 3 hours. The reaction mixture is then concentrated to dryness in vacuo, 200 ml of methanol are added to the residue and the whole is heated for 2 hours under reflux. Concentration is repeated, and the residue is taken up in 200 ml of 2N sodium hydroxide solution and extracted three times with chloroform. The combined organic phases are dried over magnesium sulphate, filtered and concentrated by evaporation. The resulting crude material is purified by chromatography over 200 g of silca gel using methylene chloride/methanol/ammonia in a ratio of 100:10:1. The fractions containing the desired product are combined and concentrated by evaporation. The residue is taken up in 50 ml of methanol and, while cooling, the pH is adjusted to 3 using hydrochloric acid. Ether is then added, the hydrochloride crystallising out. 4-chloro-5-cyano-N-(2-ethylaminoethyl)-2-methoxybenzamide hydrochloride having a melting point of 190° -192° C. is obtained.

Provenance & Evidence