Lithium Chloride → HCID 14419434, compound

HRID 2183934Notes

Reaction equation

HRID 2183934 reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[F:8].C([Sn](CCCC)(CCCC)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)CCC.[Cl-].[Li+]>O1CCCC1.[Cu]I>[F:10][C:3]1[C:2]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[C:7]([F:8])[CH:6]=[CH:5][C:4]=1[NH2:9]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 6077842-(Tributylstannyl)pyridineHCID 137327463-Bromo-2,4-difluoroaniline

Product 1

HCID 14419434HCID 14419434, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-bromo-2,4-difluorophenylamine (5.2 g, 25 mmol), 2-tri-n-butylstannylpyridine (11.0 g, 30 mmol), lithium chloride (10.6 g, 250 mmol) and copper(I) iodide (476 mg, 2.5 mmol) in tetrahydrofuran (100 ml) was degassed with nitrogen for 20 min before adding tetrakis(triphenylphosphine)palladium(0). The reaction was then heated at reflux for 5 days. The mixture was cooled to ambient temperature then partitioned between ethyl acetate and 10% ammonium hydroxide. The organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica eluting with isohexane (containing 0.5% triethylamine) on a gradient of ethyl acetate (20-50%) gave 2,4-difluoro-3-(pyridin-2-yl)phenylamine as a brown oil (550 mg, 11%): δH (400 MHz, CDCl3) 3.65 (2H, br), 6.74-6.84 (2H, m), 7.31 (1H, ddd, J 7, 5 and 1), 7.46-7.51 (1H, m), 7.78 (1H, ddd, J 8, 8 and 2), 8.74-8.77 (1H, m); m/z (ES+) 207 (M++H).

Workup

  1. customwas degassed with nitrogen for 20 min
  2. additionbefore adding tetrakis(triphenylphosphine)palladium(0)
  3. temperatureThe reaction was then heated
  4. temperatureat reflux for 5 days
  5. customthen partitioned between ethyl acetate and 10% ammonium hydroxide
  6. washThe organics were washed with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered and pre-adsorbed onto silica
  9. customPurification by chromatography on silica eluting with isohexane (containing 0.5% triethylamine) on a gradient of ethyl acetate (20-50%)

Sources & evidence

ORD record
ord-fd3637da21f246a9b59e757640d27cba
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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