Methylamine → 3-Fluoro-n,4-dimethylaniline

HRID 594802Notes

Reaction equation

HRID 594802 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([F:9])[CH:3]=1.CC([O-])=O.[K+].[CH3:15][NH2:16]>CN(C=O)C.[Cu]I>[F:9][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[CH3:8])[NH:16][CH3:15]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 1710404-Bromo-2-fluorotolueneHCID 517044Potassium Acetate

Product 1

HCID 213545073-Fluoro-n,4-dimethylanilineYield 42%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a suspension of 4-bromo-2-fluoro-1-methylbenzene (1.0 g, 5.3 mmol), KOAc (1.3 g, 13.2 mmol), and CuI (1.2 g, 6.4 mmol) in DMF (20 mL) was added methylamine (26.5 mL, 2.0M in THF, 53.0 mmol) at r.t. under N2. The reaction was stirred at 100° C. overnight in a sealed tube. The reaction mixture was filtered, diluted with water (50 mL), and extracted with EtOAc (50 mL×3). The organic layers were washed with ammonium hydroxide (50 mL×3) and brine (50 mL), dried (Na2SO4), and concentrated. The residue was purified by silica gel chromatography (PE:EtOAc=20:1) to give 310 mg (42%) of the title compound as a yellow oil. [M+H] Calc'd for C8H10FN, 140. Found, 140.

Workup

  1. filtrationThe reaction mixture was filtered
  2. additiondiluted with water (50 mL)
  3. extractionextracted with EtOAc (50 mL×3)
  4. washThe organic layers were washed with ammonium hydroxide (50 mL×3) and brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (PE:EtOAc=20:1)

Sources & evidence

ORD record
ord-17fe2d72cd7a44c0a1aabb1358a82752
Source dataset
uspto-grants-2016_01
Patent number
US09242968B2

Reaction notes

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