Dimethyl Sulfate → HCID 70453280, compound

HRID 1285358Notes

Reaction equation

HRID 1285358 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])[N:13]([CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])[C:12]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:11]=3[S:10]2)=[CH:5][CH:4]=1.[H-].[Na+].S(OC)(O[CH3:34])(=O)=O>C1C=CC=CC=1>[ClH:27].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@@H:15]([O:16][CH3:34])[C:14](=[O:17])[N:13]([CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])[C:12]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:11]=3[S:10]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 11004065HCID 11004065, compound

Product 1

HCID 70453280HCID 70453280, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 1.5 g of (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(dimethylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, 0.22 g of sodium hydride (62.2% oil dispersion) and 45 ml of benzene is refluxed for one hour. After cooling, 0.53 g of dimethyl sulfate is added to the mixture, and the mixture is stirred at room temperature for 68 hours. The mixture is further stirred at 50° C. for 3 hours. The reaction mixture is washed with an aqueous 10% sodium hydroxide solution and water, successively. The washed solution is dried and evaporated under reduced pressure to remove solvent. The residue is purified by silica gel chromatography (solvent, chloroform:ethanol (9:1)), converted into its hydrochloride and then recrystallized from a mixture of ethanol and ether. 0.7 g of (+)-cis-2-(4-methoxyphenyl)-3-methoxy-5-[2-(dimethylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one hydrochloride is obtained.

Workup

  1. temperatureis refluxed for one hour
  2. temperatureAfter cooling
  3. stirringThe mixture is further stirred at 50° C. for 3 hours
  4. washThe reaction mixture is washed with an aqueous 10% sodium hydroxide solution and water
  5. customThe washed solution is dried
  6. customevaporated under reduced pressure
  7. customto remove solvent
  8. customThe residue is purified by silica gel chromatography (solvent, chloroform:ethanol (9:1))
  9. customrecrystallized from a mixture of ethanol and ether

Sources & evidence

ORD record
ord-9fcb19b06f0142ada2a35b6b5f6b70a2
Source dataset
uspto-grants-1986_01
Patent number
US04567175

Reaction notes

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