Potassium Carbonate → 3-(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine

HRID 1480629Notes

Reaction equation

HRID 1480629 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=1.[C:12]([C:16]1[CH:17]=[CH:18][C:19]([O:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])=[C:20](B(O)O)[CH:21]=1)([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([C:16]1[CH:17]=[CH:18][C:19]([O:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])=[C:20]([C:2]2[N:3]=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=2)[CH:21]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 282425263-Chloro-6-(trifluoromethyl)pyridazineHCID 86718562(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)boronic acid2×

Product 1

HCID 867185903-(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazineYield 88%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-chloro-6-trifluoromethylpyridazine [purchased from Combi-Blocks] (250 mg, 1.37 mmol), (5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)boronic acid [Intermediate 7] (463.8 mg, 1.64 mmol) and potassium carbonate (284.5 mg, 2.06 mmol) in dimethoxyethane (7.5 mL) and water (2.5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (79.1 mg, 0.068 mmol) was added and the reaction mixture heated to 80° C. in a sealed vial for 22 hours. The cooled reaction mixture was partitioned between ethyl acetate (50 mL) and 10% aqueous sodium carbonate solution (50 mL), the organic phase separated, washed with water (50 mL) and saturated brine (50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a brown syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes to give 3-(5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine (0.462 g, 88% yield) as a colorless syrup.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (50 mL) and 10% aqueous sodium carbonate solution (50 mL)
  4. customthe organic phase separated
  5. washwashed with water (50 mL) and saturated brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a brown syrup
  10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-51d378642bdf4ee0b455b53f6ff3cf78
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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