反应详情

A mixture of (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamide (15.46 g) and chlorobenzene (309 ml) is refluxed with heating under nitrogen atmosphere. When the reflux is started, a solution of 2-aminothiophenol (11.02 g) and ferric chloride hexahydrate (2.16 mg) in methanol (0.1 ml) is added immediately to the reaction mixture, and the mixture is stirred at the same temperature for 5 minutes to give a reaction mixture containing 3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionamide (24.24 g) [(2S,3S)/(2S,3R)=91.3/8.7]. A quarter of the mixture is obtained, and 35% hydrochloric acid (1.04 g) is added thereto. The mixture is refluxed for 13 hours to remove the solvent. The remaining chlorobenzene is evaporated from the mixture, and methanol (25 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 (4.49 g).

1. temperatureis refluxed
2. temperaturewith heating under nitrogen atmosphere
3. customto give a reaction mixture
4. customA quarter of the mixture is obtained
5. temperatureThe mixture is refluxed for 13 hours
6. customto remove the solvent
7. customThe remaining chlorobenzene is evaporated from the mixture, and methanol (25 ml)
8. additionis added to the residue
9. temperatureThe mixture is refluxed for one hour
10. temperaturefurther cooled at 3° C. overnight
11. filtrationThe precipitated crystals are collected by filtration
12. washwashed with chilled methanol
13. customdried at 50° C.