Iodine → HCID 21471453, compound

HRID 2295222Notes

Reaction equation

HRID 2295222 reaction equation
[C:1]([C:3]1[C:4]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[N:5][C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][C:8]=1[CH:9]([CH3:11])[CH3:10])#[CH:2].[I:25]I>C([SnH](CCCC)CCCC)CCC.CCOCC.CC(N=NC(C#N)(C)C)(C#N)C>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:4]2[C:3](/[CH:1]=[CH:2]/[I:25])=[C:8]([CH:9]([CH3:11])[CH3:10])[CH:7]=[C:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:5]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 2

HCID 807IodineHCID 15099591HCID 15099591, compound

Product 1

HCID 21471453HCID 21471453, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 6547AzobisisobutyronitrileCatalyst2×HCID 3283Diethyl EtherSolventHCID 5948TributylstannaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-Ethynyl-2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenylpyridine (700 mg, 2.22 mmol) (the preparation of which is described in Example 14) and AIBN (11 mg) in tri-n-butylstannyl hydride (1.40 ml) was rapidly heated to 120° C. After 5 minutes of heating, the temperature of the reaction was raised to 140° C. and approximately 12 mg of AIBN was added to the reaction mixture every 0.5 hour thereafter. After 2.5 hours, the mixture was cooled to room temperature, diluted with Et2O (20 ml) and treated with solid I2 (2.00 gm, 7.9 mmol). The dark reaction mixture was stirred for one hour, then quenched with 60 ml saturated NaHCO3 containing 4 gm Na2SO3. The layers were shaken and separated. The ethereal layer was washed with brine, dried (Na2 SO4), filtered and stripped to yield a yellow oil. The oil was chromatographed twice (Merck SiO2, 5% EtOAc in hexane (1st) then 3% EtOAc in hexane (2nd)) to (E)-2-(4-Fluorophenyl)-3-(2-iodoethenyl)-4-(1-methylethyl)-6-phenyl-pyridine as a foam which solidified (671 mg). Recrystallization of the solid from hot hexane gave 482 mg of (E)-2-(4-Fluorophenyl)-3-(2-iodoethenyl)-4-(1-methylethyl)-6-phenyl-pyridine. An additional 100 mg of 2 was obtained from the mother liquor to give a total of 582 mg (59%) product.

Workup

  1. customthe preparation of which
  2. temperatureAfter 5 minutes of heating
  3. temperaturethe temperature of the reaction was raised to 140° C.
  4. temperaturethe mixture was cooled to room temperature
  5. customThe dark reaction mixture
  6. customquenched with 60 ml saturated NaHCO3 containing 4 gm Na2SO3
  7. stirringThe layers were shaken
  8. customseparated
  9. washThe ethereal layer was washed with brine
  10. customdried (Na2 SO4)
  11. filtrationfiltered
  12. customto yield a yellow oil
  13. customThe oil was chromatographed twice (Merck SiO2, 5% EtOAc in hexane (1st)
  14. customRecrystallization of the solid from hot hexane

Sources & evidence

ORD record
ord-f0b25cc15f254e5cbf8814ab5e4dba2e
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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