Potassium Carbonate → 4-Cyano-4-[3-[4-(2-methylimidazol-1-yl)phenoxy]phenyl]-3,4,5,6-tetrahydro2H-pyran

HRID 1108110

Reaction equation

HRID 1108110 reaction equation
[CH3:1][C:2]1[N:3]([C:7]2[CH:12]=[CH:11][C:10](I)=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1.[C:14]([C:16]1([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)#[N:15].C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1>[C:14]([C:16]1([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:10]3[CH:11]=[CH:12][C:7]([N:3]4[CH:4]=[CH:5][N:6]=[C:2]4[CH3:1])=[CH:8][CH:9]=3)[CH:23]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)#[N:15]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 112871604-Cyano-4-(3-hydroxyphenyl)-3,4,5,6-tetrahydro-2H-pyranHCID 112890901-(4-iodophenyl)-2-methyl-1H-imidazole

Product 1

HCID 113603734-Cyano-4-[3-[4-(2-methylimidazol-1-yl)phenoxy]phenyl]-3,4,5,6-tetrahydro2H-pyranYield 38.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-(2-methylimidazol-1-yl)phenyl iodide (1.28 g, 4.5 mmol), 4-cyano-4-(3-hydroxyphenyl)-3,4,5,6-tetrahydro-2H-pyran (1.20 g, 5.9 mmol) and K2CO3 (4.15 g, 30 mmol) in pyridine (50 ml) was heated at 130° C., cupric oxide (636 mg, 8.0 mmol) added and the reaction mixture was heated under reflux for 2 days. The reaction mixture was cooled and filtered through a celite pad and the solids were washed with ethyl acetate (100 ml). The filtrate was concentrated in vacuo, and the resulting residue was diluted with water (100 ml) and extracted with ethyl acetate (50 ml×3). The combined organic extracts were washed with 1 N aqueous NaOH (100 ml), water (100 ml) and brine (100 ml), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography {LiChroprep NH2 (Merck), 100 g; eluted with hexane/ethyl acetate (1/1)} to afford 620 mg (38%) of the titled compound as a yellow oil.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 2 days
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered through a celite pad
  5. washthe solids were washed with ethyl acetate (100 ml)
  6. concentrationThe filtrate was concentrated in vacuo
  7. additionthe resulting residue was diluted with water (100 ml)
  8. extractionextracted with ethyl acetate (50 ml×3)
  9. washThe combined organic extracts were washed with 1 N aqueous NaOH (100 ml), water (100 ml) and brine (100 ml)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography {LiChroprep NH2 (Merck), 100 g
  13. washeluted with hexane/ethyl acetate (1/1)}

Sources & evidence

ORD record
ord-64f93b0d4fc14c01bd40747eb081d0c3
Source dataset
uspto-grants-2000_05
Patent number
US06063928

Linked notes

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