Sodium Iodide → 1-[4-Cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)ethyl]piperazine

HRID 1582773Notes

Reaction equation

HRID 1582773 reaction equation
[C:1]([C:3]([C:11]1[S:15][C:14]([C:16]#[N:17])=[CH:13][CH:12]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6]O)#[N:2].CS(Cl)(=O)=O.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]1[CH:46]=[CH:45][C:35]([O:36][CH2:37][CH2:38][N:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)=[CH:34][CH:33]=1>C(#N)C.CN(C)C=O.[Cl-].[Na+].O.C(N(CC)CC)C>[C:1]([C:3]([C:11]1[S:15][C:14]([C:16]#[N:17])=[CH:13][CH:12]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6][N:42]1[CH2:41][CH2:40][N:39]([CH2:38][CH2:37][O:36][C:35]2[CH:45]=[CH:46][C:32]([F:31])=[CH:33][CH:34]=2)[CH2:44][CH2:43]1)#[N:2]

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 8950271-[2-(4-Fluorophenoxy)ethyl]piperazineHCID 223936354-Cyano-4-(5-cyano-2-thienyl)-5-methylhexanol

Product 1

HCID 223935681-[4-Cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)ethyl]piperazine

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

4-Cyano-5-methyl-4-(2-cyano-5-thienyl)hexanol, 273 mg 1.10 mmol, was dissolved in acetonitrile 5.00 ml and cooled at 0° C. Triethylamine 0.16 ml and methane sulfonyl chloride 0.10 ml 1.21 mmol were added thereto and the temperature was raised to room temperature. After 1 hour, the mixture was partitioned by adding ether and brine. The organic layer was washed with aqueous saturated sodium bicarbonate, dried over magnesium sulfate anhydride and evaporated. A half about 0.55 mmol of the residues was dissolved in N,N-dimethylformamide 5.00 ml, and 500 mg 3.34 mmol of sodium iodide, 76.0 mg 0.55 mmol of potassium carbonate, and 202 mg 0.90 mmol of 1-[2-(4-fluorophenoxy)ethyl]piperazine were added thereto, and the mixture was heated at 60° C. Brine was added to the reaction mixture which was then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate anhydride, and evaporated. The residue was purified by Chromatorex NH silica gel column chromatography (ethyl acetate/hexane system), whereby the title compound, 215 mg 0.47 mmol, 86.0%, was obtained as a yellow syrup.

Workup

  1. temperaturethe temperature was raised to room temperature
  2. customthe mixture was partitioned
  3. additionby adding ether and brine
  4. washThe organic layer was washed with aqueous saturated sodium bicarbonate
  5. dry with materialdried over magnesium sulfate anhydride
  6. customevaporated
  7. temperaturethe mixture was heated at 60° C
  8. extractionwas then extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate anhydride
  11. customevaporated
  12. customThe residue was purified by Chromatorex NH silica gel column chromatography (ethyl acetate/hexane system), whereby the title compound, 215 mg 0.47 mmol, 86.0%
  13. customwas obtained as a yellow syrup

Sources & evidence

ORD record
ord-ce599b00cccb4b2783ffb728be43d65a
Source dataset
uspto-grants-2004_05
Patent number
US06737425B1

Reaction notes

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