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

HRID 1457252Notes

Reaction equation

HRID 1457252 reaction equation
COC1C=CC([C@@H]2O[C@H]2C(N)=O)=CC=1.ClC1C=CC=CC=1.NC1C=CC=CC=1S.N[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37][CH:38]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=1)[CH:39]([OH:43])[C:40]([NH2:42])=[O:41]>CO>[OH:43][C@H:39]1[C:40](=[O:41])[NH:42][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[S:37][C@H:38]1[C:44]1[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=1

Participants

6

Reactant 4

HCID 7964ChlorobenzeneHCID 87132-AminothiophenolHCID 10821599(2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamideHCID 538426453-(2-Aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionamide

Product 1

HCID 27336733-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-Yield 81.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamide (1.93 g) and chlorobenzene (39 ml) is refluxed with heating under nitrogen atmosphere. When the reflux is started, a solution of 2-aminothiophenol (1.38 g) and ferric chloride hexahydrate (0.27 mg) in methanol (0.05 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 (3.08 g) [(2S,3S)/(2S,3R)=91.3/8.7]. The resulting reaction mixture is concentrated to 16 g. The concentrated mixture is refluxed for 13 hours during which thereto is added methanesulfonic acid (38 mg) in 5 portions (38 mg×5) at intervals of 2-3 hours. The remaining chlorobenzene is evaporated from the mixture, and methanol (10 ml) is added to the residue. The mixture is refluxed for one hour, allowed to cool to room temperature, and further cooled at 8° C. for 40 hours. 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 (2.38 g).

Workup

  1. temperatureis refluxed
  2. temperaturewith heating under nitrogen atmosphere
  3. customto give a reaction mixture
  4. customThe resulting reaction mixture
  5. concentrationis concentrated to 16 g
  6. temperatureThe concentrated mixture is refluxed for 13 hours during which
  7. additionthereto is added methanesulfonic acid (38 mg) in 5 portions (38 mg×5) at intervals of 2-3 hours
  8. customThe remaining chlorobenzene is evaporated from the mixture, and methanol (10 ml)
  9. additionis added to the residue
  10. temperatureThe mixture is refluxed for one hour
  11. temperaturefurther cooled at 8° C. for 40 hours
  12. filtrationThe precipitated crystals are collected by filtration
  13. washwashed with chilled methanol
  14. customdried at 50° C.

Sources & evidence

ORD record
ord-27ddb937ae394f93b0f9a928fd8d1a07
Source dataset
uspto-grants-1998_12
Patent number
US05847122

Reaction notes

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