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

HRID 1457253Notes

Reaction equation

HRID 1457253 reaction equation
COC1C=CC([C@@H]2O[C@H]2C(N)=O)=CC=1.NC1C=CC=CC=1S.N[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[S:30][CH:31]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1)[CH:32]([OH:36])[C:33]([NH2:35])=[O:34].Cl>CO.ClC1C=CC=CC=1>[OH:36][C@H:32]1[C:33](=[O:34])[NH:35][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:30][C@H:31]1[C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 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 19.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7964ChlorobenzeneSolvent

Procedure

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).

Workup

  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.

Sources & evidence

ORD record
ord-b74fd088aa3f4f84ab3845dcb76904ab
Source dataset
uspto-grants-1998_12
Patent number
US05847122

Reaction notes

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