Sodium Iodide → (4-Cyano-5-methyl-4-(5-cyano-2-thienyl)hexyl]-4-[2-(3-cyanophenoxy)ethyl]piperazine

HRID 1071649Notes

Reaction equation

HRID 1071649 reaction equation
[C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6]O)#[N:2].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[C:38]([C:40]1[CH:41]=[C:42]([CH:52]=[CH:53][CH:54]=1)[O:43][CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)#[N:39]>C(#N)C.[Cl-].[Na+].O.CN(C)C=O.CCOCC>[C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6][N:49]1[CH2:48][CH2:47][N:46]([CH2:45][CH2:44][O:43][C:42]2[CH:52]=[CH:53][CH:54]=[C:40]([C:38]#[N:39])[CH:41]=2)[CH2:51][CH2:50]1)#[N:2]

Participants

11

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 223936354-Cyano-4-(5-cyano-2-thienyl)-5-methylhexanolHCID 223936831-(3-Cyanophenoxyethyl)piperazine

Product 1

HCID 10161766(4-Cyano-5-methyl-4-(5-cyano-2-thienyl)hexyl]-4-[2-(3-cyanophenoxy)ethyl]piperazineYield 77.3%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
0 °C

Procedure

In acetonitrile (10.0 ml) was dissolved 400 mg (1.61 mmol) of 4-cyano-5-methyl-4-(5-cyano-2-thienyl)hexanol, followed by cooling to 0° C. To the mixture were added 0.26 ml (1.85 mmol) of triethylamine and 0.14 ml (1.77 mmol) of mesyl chloride, followed by heating to room temperature. After 20 minutes, ether and brine were added thereto. The ether layer was washed with an aqueous saturated sodium bicarbonate and dried over anhydrous magnesium sulfate. The solvent was evaporated, to give a crude product. The half amount (ca. 0.1 mmol) of the crude mesyl compound was dissolved in 8.00 ml of dimethylformamide. To the mixture were added 724 mg (4.83 mmol) of sodium iodide, ill mg (0.81 mmol) of potassium carbonate and 243 mg (1.05 mmol) of 1-[2-(3-cyanophenoxy)ethyl]piperazine, followed by heating to 60° C. After completion of the reaction, brine was added thereto, and the objective product was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to give a crude product. The crude product was subjected to Cromatorex NH silica gel (eluted with ethyl acetate/hexane=1/1), to give 289 mg (0.63 mmol, 77.3%) of the title compound as a yellow syrup.

Workup

  1. temperatureby heating to room temperature
  2. washThe ether layer was washed with an aqueous saturated sodium bicarbonate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customto give a crude product
  6. temperatureby heating to 60° C
  7. additionwas added
  8. extractionthe objective product was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated
  12. customto give a crude product

Sources & evidence

ORD record
ord-86f813d40c0f4e71b8735832510cefeb
Source dataset
uspto-grants-2005_06
Patent number
US06906072B1

Reaction notes

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