Ethyl Acetate → 4'-Chloro-3-fluoro[1,1'-biphenyl]-4-amine

HRID 734998Notes

Reaction equation

HRID 734998 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](OB(O)O)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1.C(OCC)(=O)C>CO.O.O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:19]2[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 1230504-Bromo-2-fluoroanilineHCID 17810664p-Chlorophenylboric acid

Product 1

HCID 200996184'-Chloro-3-fluoro[1,1'-biphenyl]-4-amine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

1.95 g (12.47 mmol) of 4-chlorophenylboric acid, dissolved in 10 mL of methanol, and 3.9 g (36.79 mmol) of sodium carbonate, dissolved in 10 mL of water, are added successively to a reaction mixture of 2.28 g (12 mmol) of 4-bromo-2-fluoroaniline and 0.6 g (0.51 mmol) of tetrakistriphenylphosphine palladium in 90 mL of dioxane and stirred for 14 hours at 80° C. Then ethyl acetate is added and the reaction mixture is filtered. The filtrate is evaporated down and extracted with ethyl acetate and water. The organic phase is dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluant: cyclohexane/ethyl acetate (3:1)). Yield: 2 g (75.2% of theory); C12H9FN (M=221.66); calc.: molecular ion peak (M+H)+: 222; found: molecular ion peak (M+H)+: 222; Rf value: 0.41 (silica gel, cyclohexane/ethyl acetate (3:1)).

Workup

  1. filtrationthe reaction mixture is filtered
  2. customThe filtrate is evaporated down
  3. extractionextracted with ethyl acetate and water
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. customThe purification

Sources & evidence

ORD record
ord-06f60839a67a4ad194949ce9382ffe3d
Source dataset
uspto-grants-2009_09
Patent number
US07592373B2

Reaction notes

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