Sodium hydride → N-[2-(3,4-Dimethoxyphenyl)ethyl]-alpha-{2-chloro-4-[2-(ethoxycarbonylamino)propionyl]phenoxy}acetamide

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Reaction Steps

505 mg of ethyl N-[2-(3-chloro-4-hydroxyphenyl)-1-methyl-2-oxoethyl]carbamate [prepared as described in step (b) above] were added to a suspension of 81 mg of sodium hydride (as a 55% w/w suspension in mineral oil) in 6 ml of anhydrous dimethylformamide, whilst ice-cooling. The mixture was then stirred at room temperature for 1 hour. The suspension was then cooled, and 476 mg of α-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide (prepared as described in Preparation 1) were added thereto. The mixture was stirred at room temperature for 2 hours and then at 100° C. (bath temperature) for 3 hours. At the end of this time, the dimethylformamide used as the solvent was removed by evaporation under reduced pressure, and water was added to the residue. The aqueous mixture was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride, dried and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography through silica gel. After elution of impurities with a 2:1 by volume mixture of ethyl acetate and hexane, 556 mg of the title compound were obtained from the fractions eluted with ethyl acetate as a pale yellow powder melting at 113°-114° C.

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