Triethylamine → HCID 89873978, compound

HRID 715415Notes

Reaction equation

HRID 715415 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[C:4]([CH3:14])[CH:3]=1.Cl[C:16]1[N:17]=[N:18][C:19]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:20][C:21]=1[CH3:22].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH3:65][CH2:66][O:67][C:68](C)=[O:69]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCO.CN(C=O)C>[CH3:14][C:4]1[CH:3]=[C:2]([C:68]([O:67][CH2:66][CH3:65])=[O:69])[N:7]=[N:6][C:5]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[CH3:22][C:21]1[CH:20]=[C:19]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[N:18]=[N:17][C:16]=1[C:68]([O:67][CH2:66][CH3:65])=[O:69]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 89874011HCID 89874011, compoundHCID 89874021HCID 89874021, compound

Product 2

HCID 89873978HCID 89873978, compoundHCID 89874066HCID 89874066, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-4-methyl-3-(2,2,2-trifluoroethoxy)pyridazine and 3-chloro-4-methyl-6-(2,2,2-trifluoroethoxy)pyridazine (3.40 g, 15.0 mmol, Step-1), palladium(II) acetate (0.34 g, 1.50 mmol), 1,3-bis(diphenylphosphino)propane (1.24 g, 3.00 mmol), triethylamine (6.27 mL, 45.0 mmol), DMF (40 mL), and EtOH (20 mL) is stirred at 80° C. under carbon monoxide atmosphere (1 atm) for 20 hours. After cooling to rt, the mixture is diluted with EtOAc (200 mL). This is washed with water (200 mL×2), and the organic layer is dried over sodium sulfate. After removal of the organic solvent, the residue is purified by column chromatography on silica-gel eluting with n-hexane/EtOAc (8:1-5:1) to give 2.15 g of ethyl 5-methyl-6-(2,2,2-trifluoroethoxy)pyridazine-3-carboxylate (54% yield, more polar product) as an off-white solid and 0.63 g of ethyl 4-methyl-6-(2,2,2-trifluoroethoxy)pyridazine-3-carboxylate (16% yield, less polar product) as pale yellow oil.

Workup

  1. temperatureAfter cooling to rt
  2. washThis is washed with water (200 mL×2)
  3. dry with materialthe organic layer is dried over sodium sulfate
  4. customAfter removal of the organic solvent
  5. customthe residue is purified by column chromatography on silica-gel
  6. washeluting with n-hexane/EtOAc (8:1-5:1)

Sources & evidence

ORD record
ord-dd0d0d125423472b966691159a351a61
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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