p-Toluenesulfonic acid monohydrate → 3-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-

HRID 1457249Notes

Reaction equation

HRID 1457249 reaction equation
NC1C=CC=CC=1[S:8][C@@H:9]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)[C@@H:10]([OH:20])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:12].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClC1C=CC=CC=1>[OH:20][C@H:10]1[C:11](=[O:12])[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:8][C@H:9]1[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 57060229HCID 57060229, compound

Product 1

HCID 27336733-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-Yield 54.7%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Procedure

(2S,3S)-3-(2-Aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)-N-phenylpropionamide (582 mg) is mixed with chlorobenzene (10 ml), and the mixture is refluxed for 25 hours during which thereto is added p-toluenesulfonic acid monohydrate (112 mg) in 8 portions (14 mg×8) at intervals of three hours. The reaction mixture is cooled to room temperature, and concentrated under reduced pressure to remove the chlorobenzene. To the residue is added methanol (5 ml), and the mixture is refluxed for one hour. The mixture is allowed to cool to room temperature, and stirred to crystallization, and then cooled with ice. 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 (243 mg).

Workup

  1. temperaturethe mixture is refluxed for 25 hours during which
  2. concentrationconcentrated under reduced pressure
  3. customto remove the chlorobenzene
  4. additionTo the residue is added methanol (5 ml)
  5. temperaturethe mixture is refluxed for one hour
  6. temperatureto cool to room temperature
  7. temperaturecooled with ice
  8. filtrationThe precipitated crystals are collected by filtration
  9. washwashed with chilled methanol
  10. customdried at 50° C.

Sources & evidence

ORD record
ord-633672b60d42404ca9695ea659e527bb
Source dataset
uspto-grants-1998_12
Patent number
US05847122

Reaction notes

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