Iodine → HCID 49761587, compound

HRID 1948626Notes

Reaction equation

HRID 1948626 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[N:7][CH:8]=1.CN(CCN(C)C)C.[Li]CCCC.[I:31]I>C1COCC1>[I:31][C:5]1[C:6]([NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:13])[CH3:14])=[N:7][CH:8]=[C:3]([C:2]([F:16])([F:1])[F:17])[CH:4]=1

Participants

6

Reactant 4

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 58563823N-(5-(trifluoromethyl)pyridin-2-yl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 49761587HCID 49761587, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

N-(5-(trifluoromethyl)pyridin-2-yl)pivalamide (22 g, 89.4 mmole) and TMEDA (33.3 ml, 223.4 mmole) were dissolved in THF (400 ml) under nitrogen and n-BuLi (139.6 ml, 223.4 mmole; 1.6 M solution in n-hexane) was added dropwise at −75° C. The mixture was stirred for 2 hours at −75° C. While maintaining this temperature a solution of iodine (56.7 g, 223.4 mmole) in THF (280 ml) was added dropwise and the reaction mixture was stirred for 2 hours. The reaction mixture was heated to 0° C. and quenched with saturated aqueous sodium thiosulfate solution. The aqueous phase was extracted with DCM (2×150 ml) and the combined organic phases were dried over MgSO4. After filtering off the drying agent and removing the solvent on a rotary evaporator the residue was purified by means of column chromatography (ether: cyclohexane=1:1) and N-(3-iodo-5-(trifluoromethyl)pyridin-2-yl)pivalamide (13 g, 39.1%) was thereby obtained.

Workup

  1. additionwas added dropwise
  2. stirringthe reaction mixture was stirred for 2 hours
  3. temperatureThe reaction mixture was heated to 0° C.
  4. customquenched with saturated aqueous sodium thiosulfate solution
  5. extractionThe aqueous phase was extracted with DCM (2×150 ml)
  6. dry with materialthe combined organic phases were dried over MgSO4
  7. filtrationAfter filtering off the drying agent
  8. customremoving the solvent
  9. customon a rotary evaporator the residue
  10. customwas purified by means of column chromatography (ether: cyclohexane=1:1) and N-(3-iodo-5-(trifluoromethyl)pyridin-2-yl)pivalamide (13 g, 39.1%)
  11. customwas thereby obtained

Sources & evidence

ORD record
ord-96ca041df1724a77a2b8b723ec0c1dfa
Source dataset
uspto-grants-2013_03
Patent number
US08399503B2

Reaction notes

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