Acetone → (2S-cis)-5-(2-(Dimethylamino)ethyl)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one monohydrochloride

HRID 1903701Notes

Reaction equation

HRID 1903701 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[NH:13][C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:5][CH:4]=1.Cl.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][Cl:27].C(=O)([O-])[O-].[K+].[K+].CC(C)=O>O>[ClH:27].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[N:13]([CH2:26][CH2:25][N:24]([CH3:28])[CH3:23])[C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 11430Potassium CarbonateHCID 27336733-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-HCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 12449428(2S-cis)-5-(2-(Dimethylamino)ethyl)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one monohydrochlorideYield 90.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 30.1 g of cis-(+)-2-(4-methoxyphenyl)-3-hydroxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one, 17.2 g of 2-(dimethylamino)ethyl chloride hydrochloride, 31.8 g of potassium carbonate and 240 ml of acetone is refluxed for 30 minutes after stirring. Then, 10 ml of water are added to the mixture, and the aqueous mixture is further refluxed for 3 hours under stirring. After the reaction is completed, the mixture is evaporated under reduced pressure to remove acetone. The residue is dissolved in toluene, and the solution is washed twice with water. The toluene layer is collected and then evaporated under reduced pressure to remove toluene. The residue is dissolved in ethanol. After cooling the solution, said solution is acidified with 10% HCl/ethanol and then stirred at a temperature below 5° C. for 5 hours. The crystalline precipitates are collected by filtration, washed with ethanol and then dried. 37.1 g of cis-(+)-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-1,5-benzothiazepine-4(5H)-one hydrochloride are thereby obtained. Yield: 90.7%

Workup

  1. temperatureis refluxed for 30 minutes
  2. temperaturethe aqueous mixture is further refluxed for 3 hours
  3. stirringunder stirring
  4. customthe mixture is evaporated under reduced pressure
  5. customto remove acetone
  6. dissolutionThe residue is dissolved in toluene
  7. washthe solution is washed twice with water
  8. customThe toluene layer is collected
  9. customevaporated under reduced pressure
  10. customto remove toluene
  11. dissolutionThe residue is dissolved in ethanol
  12. temperatureAfter cooling the solution
  13. stirringstirred at a temperature below 5° C. for 5 hours
  14. customThe crystalline precipitates
  15. filtrationare collected by filtration
  16. washwashed with ethanol
  17. customdried

Sources & evidence

ORD record
ord-3eeefcbe86394e2bb449e46b3080206d
Source dataset
uspto-grants-1984_03
Patent number
US04438035

Reaction notes

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