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

A mixture of (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamide (3.86 g) and chlorobenzene (77 ml) is refluxed with heating under nitrogen atmosphere. When the reflux is started, a solution of 2-aminothiophenol (2.75 g) and ferric chloride hexahydrate (0.54 mg) in methanol (0.1 ml) is added immediately into the reaction mixture, and the mixture is reacted at the same temperature for 5 minutes. The reaction mixture is subjected to HPLC analysis* to confirm the production of 3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionamide (6.09 g) [(2S,3S)/(2S,3R)=91.5/8.5]. To the reaction mixture is added p-toluenesulfonic acid monohydrate (0.76 g), and the mixture is refluxed for 32 hours, and concentrated under reduced pressure to remove the chlorobenzene. To the residue is added methanol (25 ml), and the mixture is refluxed for one hour, and cooled with ice overnight. The precipitated crystals are collected by filtration, washed with methanol, and dried at 50° C. to give (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (4.76 g).

1. temperatureis refluxed
2. temperaturewith heating under nitrogen atmosphere
3. customthe mixture is reacted at the same temperature for 5 minutes
4. temperaturethe mixture is refluxed for 32 hours
5. concentrationconcentrated under reduced pressure
6. customto remove the chlorobenzene
7. additionTo the residue is added methanol (25 ml)
8. temperaturethe mixture is refluxed for one hour
9. temperaturecooled with ice overnight
10. filtrationThe precipitated crystals are collected by filtration
11. washwashed with methanol
12. customdried at 50° C.

ORD record

ord-b5c08fa0d8e84286b9c2482b456ce7f0

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05847122