2-Chloro-N,N-dimethylethylamine → 3-(Acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one

Participants

Reaction Steps

5-(1). 2-(4'-Methoxyphenyl)-3-acetoxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one [Compound (II)] (1.0 g) and dried silica gel suitable for column chromatography (which is obtained by calcining a commercially available silica gel (Wako gel C-200) at 300° C. under nitrogen for 8 hours) (0.5 g) are added to dimethylsulfoxide (10 ml), and thereto is added a 60% by weight sodium hydride (0.14 g), and the mixture is stirred at room temperature for 30 minutes. A 50% by weight solution (0.75 g) of N,N-dimethylaminoethyl chloride in ether is added to the mixture, and the mixture is further stirred at room temperature for 5 hours and neutralized with acetic acid, and then, silica gel is filtered off. To the filtrate is added benzene, and the benzene solution is washed with water, dried, and evaporated to remove benzene to give a solid substance (1.20 g). The solid substance is added to diisopropyl ether. After removing the insoluble materials by filtration, the filtrate is allowed to stand at room temperature. The precipitated crystals are separated by filtration to give the title compound (I) (0.92 g, 76.2%), m.p. 134°-135° C. The hydrochloride of this product: m.p. 187°-188° C.

Provenance & Evidence