Potassium Iodide → HCID 67605616, compound

HRID 362789Notes

Reaction equation

HRID 362789 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([O:13][C@H:14]2[CH2:19][CH2:18][NH:17][CH2:16][C@H:15]2[O:20][CH3:21])=[O:12])=[CH:4][C:3]=1[Cl:22].Cl[CH2:24][CH2:25][CH2:26][C:27]([C:29]1[CH:34]=[C:33]([O:35][CH3:36])[C:32]([O:37][CH3:38])=[C:31]([O:39][CH3:40])[CH:30]=1)=[O:28].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CC(C)CC(=O)C>[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([O:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH2:24][CH2:25][CH2:26][C:27](=[O:28])[C:29]3[CH:30]=[C:31]([O:39][CH3:40])[C:32]([O:37][CH3:38])=[C:33]([O:35][CH3:36])[CH:34]=3)[CH2:16][C@H:15]2[O:20][CH3:21])=[O:12])=[CH:4][C:3]=1[Cl:22]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 54408345HCID 54408345, compoundHCID 86753730HCID 86753730, compound

Product 1

HCID 67605616HCID 67605616, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of intermediate (6) (2.3 g), 4-chloro-1-(3,4,5-trimethoxyphenyl)-1-butanone (2 g), sodium carbonate (2.1 g) and potassium iodide (catalytic quantity) in 4-methyl-2-pentanone (150 ml; previously dried over MgSO4) was stirred and refluxed overnight. The reaction mixture was cooled, washed with water, dried over MgSO4, filtered and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2, upgrading to CH2Cl2 /(CH3OH/NH3) 97/3). The pure fractions were collected and the solvent was evaporated. The residue was dissolved in methanol and converted into the ethanedioic acid salt with ethanedioic acid (0.6 g). The mixture was boiled, then cooled and the precipitate was filtered off and recrystallized from 2-propanol. The precipitate was dissolved in aqueous NH4OH/CH2Cl2. The organic layer was separated, dried over MgSO4, filtered and the solvent was evaporated. The residue was stirred in boiling diisopropylether, cooled and the resulting precipitate was filtered off and dried (vacuum; 80° C.), yielding 1.10 g of (±)-cis-3-methoxy-1-[4-oxo-4-(3,4,5-trimethoxyphenyl)butyl]-4-piperidinyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate (28%); mp. 132.3° C. (compound 1). In a similar manner there were also prepared:

Workup

  1. dry with materialpreviously dried over MgSO4)
  2. temperaturerefluxed overnight
  3. temperatureThe reaction mixture was cooled
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2, upgrading to CH2Cl2 /(CH3OH/NH3) 97/3)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. dissolutionThe residue was dissolved in methanol
  12. temperaturecooled
  13. filtrationthe precipitate was filtered off
  14. customrecrystallized from 2-propanol
  15. dissolutionThe precipitate was dissolved in aqueous NH4OH/CH2Cl2
  16. customThe organic layer was separated
  17. dry with materialdried over MgSO4
  18. filtrationfiltered
  19. customthe solvent was evaporated
  20. stirringThe residue was stirred
  21. temperaturecooled
  22. filtrationthe resulting precipitate was filtered off
  23. customdried (vacuum; 80° C.)

Sources & evidence

ORD record
ord-48d94754f4c04f08903679bee221eebb
Source dataset
uspto-grants-1999_02
Patent number
US05872131

Reaction notes

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