2-Aminothiophenol → 3-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-

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Reaction Steps

A mixture of (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamide (9.66 g) and chlorobenzene (193 ml) is refluxed with heating under nitrogen atmosphere. When the reflux is started, a solution of 2-aminothiophenol (6.89 g) and ferric chloride hexahydrate (1.35 mg) in methanol (0.1 ml) is added immediately into the reaction mixture, and the mixture is stirred at the same temperature for 5 minutes. The reaction mixture containing (2S,3S)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionamide is refluxed for 15 hours during which p-toluenesulfonic acid monohydrate (2.88 g) is added thereto in 6 portions (0.48 g×6) at intervals of 2.5 hours to remove the chlorobenzene. The remaining chlorobenzene is evaporated, and methanol (50 ml) is added to the residue. The mixture is refluxed for one hour, allowed to cool to room temperature, and further cooled at 3° C. overnight. The precipitated crystals are collected by filtration, washed with chilled methanol, and dried at 50° C. to give (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (11.73 g).

Provenance & Evidence