Ammonia → 3-Methyl-6-(trifluoromethyl)pyridazine

HRID 420706Notes

Reaction equation

HRID 420706 reaction equation
[F-].[K+].N#N.I[C:6]1[N:7]=[N:8][C:9]([CH3:12])=[CH:10][CH:11]=1.C[Si](C)(C)[C:15]([F:18])([F:17])[F:16].N>CN(C=O)C.CN1CCCC1=O.[Cu]I.CC(OC)(C)C>[CH3:12][C:9]1[N:8]=[N:7][C:6]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1

Participants

10

Reactant 5

HCID 222AmmoniaHCID 947NitrogenHCID 522689Potassium Fluoride3×HCID 552549(Trifluoromethyl)trimethylsilane3×HCID 126802583-Iodo-6-methylpyridazine

Product 1

HCID 206919503-Methyl-6-(trifluoromethyl)pyridazineYield 35%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst3×HCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A mixture of CuI (263 mg) and KF (80 mg) was heated under vacuum for 30 minutes until a greenish colour was observed. The system was filled with N2 and a solution of 3-iodo-6-methylpyridazine (300 mg) in DMF (1.25 ml) and N-methylpyrrolidinone (1.25 ml) followed by trimethyl(trifluoromethyl)silane (185 μl) were subsequently added. A dark brown colour was observed. After stirring at room temperature for 5 days, the reaction was not complete. CuI (263 mg), KF (80 mg), and CF3TMS (185 μl) were added and stirring was continued overnight. Additional CuI (135 mg), KF (40 mg), and CF3TMS (90 μl) were added and after one more day at room temperature, almost no starting material was observed. Aqueous ammonia and TBME were added and the phases were separated. The aqueous one was washed with TBME. The organic extracts were combined and subsequently washed with aqueous ammonia, 1M HCl, saturated NaHCO3, and brine, dried over Na2SO4, filtered and concentrated to give 70 mg (35%) of the title compound.

Workup

  1. temperaturewas heated under vacuum for 30 minutes until a greenish colour
  2. additionwere subsequently added
  3. stirringstirring
  4. waitwas continued overnight
  5. customat room temperature
  6. customthe phases were separated
  7. washThe aqueous one was washed with TBME
  8. washsubsequently washed with aqueous ammonia, 1M HCl, saturated NaHCO3, and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e0775923dc634929892d6ae70ddd55ca
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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