Cesium fluoride → 2-Pyridazin-4-yl-4-(trifluoromethoxy)phenol

HRID 2283645Notes

Reaction equation

HRID 2283645 reaction equation
I[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[OH:13].C([Sn](CCCC)(CCCC)[C:19]1[CH:24]=[CH:23][N:22]=[N:21][CH:20]=1)CCC.[F-].[Cs+]>CN(C)C=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.[Cu]I>[N:21]1[CH:20]=[CH:19][C:24]([C:2]2[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=2[OH:13])=[CH:23][N:22]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 27694112-Iodo-4-(trifluoromethoxy)phenolHCID 64097334-(Tributylstannyl)pyridazine

Product 1

HCID 1360636182-Pyridazin-4-yl-4-(trifluoromethoxy)phenol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

2-Iodo-4-(trifluoromethoxy)phenol (Preparation 29, 3.30 g, 9.99 mmol) and 4-(tributylstannyl)pyridazine (4.06 g, 11.0 mmol) were taken up in dimethylformamide (40 mL). Cesium fluoride (3.03 g, 20.0 mmol) was added followed by tetrakis(triphenylphosphine)palladium(0) (1.2 g, 1.0 mmol) and copper(I) iodide (380 mg, 2.0 mmol). The reaction mixture was evacuated and purged with argon (×5) then heated at 45° C. After 2 hours the reaction mixture was cooled and diluted with ethyl acetate and water. The mixture was filtered through a pad of diatomaceous earth and washed with ethyl acetate. The aqueous phase was separated and back extracted with ethyl acetate. The combined organic phase was concentrated in vacuo. The residue was purified by silica gel column chromatography (0% to 10% methanol in dichloromethane gradient elution) then triturated with ethyl ether. The solid was collected by filtration and dried in vacuo to afford the title compound product as a yellow solid (1.18 g, 46%).

Workup

  1. customThe reaction mixture was evacuated
  2. custompurged with argon (×5)
  3. temperatureAfter 2 hours the reaction mixture was cooled
  4. additiondiluted with ethyl acetate and water
  5. filtrationThe mixture was filtered through a pad of diatomaceous earth
  6. washwashed with ethyl acetate
  7. customThe aqueous phase was separated
  8. extractionback extracted with ethyl acetate
  9. concentrationThe combined organic phase was concentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography (0% to 10% methanol in dichloromethane gradient elution)
  11. customthen triturated with ethyl ether
  12. filtrationThe solid was collected by filtration
  13. customdried in vacuo

Sources & evidence

ORD record
ord-b4675d2ed81943f49e865fe2945fd712
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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