Ethanol → 6-[3-(4-Fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazine-3-carboxylic acid ethyl ester

HRID 402448Notes

Reaction equation

HRID 402448 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([O:8][CH2:9][C:10]2[N:11]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[N:12]=[N:13][C:14]=2[CH3:15])=[CH:6][CH:7]=1.[C:23](=[O:26])([O-])[O-:24].[Na+].[Na+].[CH2:29](O)[CH3:30]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:29]([O:24][C:23]([C:2]1[N:3]=[N:4][C:5]([O:8][CH2:9][C:10]2[N:11]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[N:12]=[N:13][C:14]=2[CH3:15])=[CH:6][CH:7]=1)=[O:26])[CH3:30]

Participants

6

Reactant 3

HCID 702EthanolHCID 10340Sodium CarbonateHCID 573356983-Chloro-6-[3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazine

Product 1

HCID 573356996-[3-(4-Fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazine-3-carboxylic acid ethyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
50 °C

Procedure

To a suspension of 3-chloro-6-[3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazine (696 mg, 2.18 mmol) in ethanol (11 mL) was added sodium carbonate (231 mg, 2.18 mmol) followed by 1,1′-bis(diphenylphosphino) ferrocene (121 mg, 0.22 mmol) and palladium(II) acetate (49 mg, 0.22 mmol). The reaction flask was filled with Ar three times after a short evacuation. The fourth time the flask was flushed with CO-gas (balloon). The mixture was stirred under CO atmosphere at 50° C. over night, then cooled to room temperature and filtered over dicalite and washed well with DCM. The filtrate was then evaporated. Purification by chromatography (silica, 0 to 50% ethyl acetate in heptane) afforded the title compound (725 mg, 93%) as a light yellow gum. MS: m/e=358.2 [M+H]+.

Workup

  1. additionThe reaction flask was filled with Ar three times after a short evacuation
  2. customThe fourth time the flask was flushed with CO-gas (balloon)
  3. temperaturecooled to room temperature
  4. filtrationfiltered over dicalite
  5. washwashed well with DCM
  6. customThe filtrate was then evaporated
  7. customPurification by chromatography (silica, 0 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-fea613fad294445fb7a724d8932d4234
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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