Toluene → 2-Fluoro-5-methyl-4-(2-methylpyridin-4-yl)aniline

HRID 592210

Reaction equation

HRID 592210 reaction equation
Br[C:2]1[C:8]([CH3:9])=[CH:7][C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[CH3:11][C:12]1[CH:17]=[C:16](B(O)O)[CH:15]=[CH:14][N:13]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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(O)C>[F:10][C:4]1[CH:3]=[C:2]([C:16]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:11])[CH:17]=2)[C:8]([CH3:9])=[CH:7][C:5]=1[NH2:6]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 70180404-Bromo-2-fluoro-5-methylaniline

Product 1

HCID 584477092-Fluoro-5-methyl-4-(2-methylpyridin-4-yl)aniline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

To a round bottom flask charged with 4-bromo-2-fluoro-5-methylaniline 191-1 (2.04 g, 10 mmol), 2-methylpyridin-4-ylboronic acid 191-2 (1.37 g, 10 mmol) and Pd(PPh3)4 (0.4 g, 0.35 mmol) was added toluene (30 mL), ethanol (10 mL) and saturated sodium carbonate (10 mL). The flask was flushed with nitrogen and the reaction was heated to reflux for 10 hours. After the reaction was cooled down to room temperature, it was partitioned between ethyl acetate and saturated NaHCO3 and the organic phase was washed with brine and dried over Na2SO4. The solvent was removed by rotary evaporation and the residue was purified by silica gel flash chromatography, eluted with 50% ethyl acetate in hexane to give 2-fluoro-5-methyl-4-(2-methylpyridin-4-yl)aniline 191-3. MS m/z 217.1 (M+1).

Workup

  1. customThe flask was flushed with nitrogen
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 10 hours
  4. customit was partitioned between ethyl acetate and saturated NaHCO3
  5. washthe organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed by rotary evaporation
  8. customthe residue was purified by silica gel flash chromatography
  9. washeluted with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c3973b6529bb4741881e2623278479f7
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Linked notes

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