Sodium Iodide → 3-(2-Ethyl-5-iodophenyl)bicyclo[3.2.1]octane-2,4-dione

HRID 72265Notes

Reaction equation

HRID 72265 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:18][CH3:19])=[C:6]([CH:8]2[C:14](=[O:15])[CH:13]3[CH2:16][CH:10]([CH2:11][CH2:12]3)[C:9]2=[O:17])[CH:7]=1.[I-:20].[Na+].C[Si](C)(C)N[Si](C)(C)C.CN[C@@H]1CCCC[C@H]1NC>[Cu]I.O1CCOCC1>[CH2:18]([C:5]1[CH:4]=[CH:3][C:2]([I:20])=[CH:7][C:6]=1[CH:8]1[C:14](=[O:15])[CH:13]2[CH2:16][CH:10]([CH2:11][CH2:12]2)[C:9]1=[O:17])[CH3:19]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 13838HexamethyldisilazaneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 666795693-(5-Bromo-2-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 684856003-(2-Ethyl-5-iodophenyl)bicyclo[3.2.1]octane-2,4-dioneYield 100%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

To a microwave vial is added 3-(5-bromo-2-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione (1.00 g, 3.11 mmol), sodium iodide (0.93 g, 6.23 mmol), hexamethyldisilazane (0.45 g, 3.11 mmol), copper(I) iodide (0.03, 0.15 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.044 g, 0.31 mmol) then degassed dioxane (5 ml). After purging with nitrogen the mixture is heated at 180° C. for 1 hour under microwave irradiation. The mixture is cooled to room temperature, quenched with 2M hydrochloric acid and extracted with dichloromethane (×2). Organic fractions are combined, washed with saturated aqueous sodium metabisulfite, dried over magnesium sulfate then filtered. The filtrate is concentrated in vacuo, then purified by flash column chromatography (20% to 100% ethyl acetate/hexane eluant ratio) to afford 3-(2-ethyl-5-iodophenyl)bicyclo[3.2.1]-octane-2,4-dione (1.14 g, 100%) as a white solid.

Workup

  1. customAfter purging with nitrogen the mixture
  2. temperatureThe mixture is cooled to room temperature
  3. customquenched with 2M hydrochloric acid
  4. extractionextracted with dichloromethane (×2)
  5. washwashed with saturated aqueous sodium metabisulfite
  6. dry with materialdried over magnesium sulfate
  7. filtrationthen filtered
  8. concentrationThe filtrate is concentrated in vacuo
  9. custompurified by flash column chromatography (20% to 100% ethyl acetate/hexane eluant ratio)

Sources & evidence

ORD record
ord-584597383866409495d5bd2f8b801da4
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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