4-(2-Iodoethyl)-1,2-dimethoxybenzene → cis-3-(Acetyloxy)-2,3,4,5-tetrahydro-2-(4-methoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]N,N-dimethyl-4-oxo-1,5-benzothiazepine-5-ethanaminium iodide

HRID 568783

Reaction equation

HRID 568783 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[CH2:6][CH2:7][I:8].[CH3:14][C:15]([O:17][C@H:18]1[C:28](=[O:29])[N:27]([CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:20][C@H:19]1[C:35]1[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=1)=[O:16].I>C(OCC)(=O)C>[I-:8].[C:15]([O:17][C@H:18]1[C:28](=[O:29])[N:27]([CH2:30][CH2:31][N+:32]([CH2:7][CH2:6][C:5]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=2)([CH3:34])[CH3:33])[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:20][C@H:19]1[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1)(=[O:16])[CH3:14]

Participants

4

Reactant 2

HCID 5970224-(2-Iodoethyl)-1,2-dimethoxybenzeneHCID 67937026Diltiazem hydroiodide

Product 1

HCID 67937057cis-3-(Acetyloxy)-2,3,4,5-tetrahydro-2-(4-methoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]N,N-dimethyl-4-oxo-1,5-benzothiazepine-5-ethanaminium iodide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a flask under argon containing 4.94 g (0.0119 mole) diltiazem was added 50 ml ethyl acetate and 3.48 g (0.0119 mole) 3,4-dimethoxyphenethyl iodide. The reaction was refluxed for 24 hr then filtered. The filtrate was washed with sodium bicarbonate and brine, dried over K2CO3, and 0.85 g 3,4-dimethoxyphenethyl iodide added and the reaction refluxed for 18 hr then filtered. The last step was repeated but 1.75 g of 3,4-dimethoxyphenethyl iodide was added and the reaction refluxed 5 hr. The filtered materials were combined and recrystallized from 95% ethanol to give a mixture of product and diltiazem hydroiodide.

Workup

  1. temperatureThe reaction was refluxed for 24 hr
  2. filtrationthen filtered
  3. washThe filtrate was washed with sodium bicarbonate and brine
  4. dry with materialdried over K2CO3, and 0.85 g 3,4-dimethoxyphenethyl iodide
  5. additionadded
  6. temperaturethe reaction refluxed for 18 hr
  7. filtrationthen filtered
  8. addition1.75 g of 3,4-dimethoxyphenethyl iodide was added
  9. temperaturethe reaction refluxed 5 hr
  10. customrecrystallized from 95% ethanol
  11. customto give

Sources & evidence

ORD record
ord-5a01193bfccd426daa6c66d5d7335ce6
Source dataset
uspto-grants-1988_03
Patent number
US04729994

Linked notes

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