2-Amino-5-bromo-3-nitropyridine → 5-(4-Fluorophenyl)-3-nitropyridin-2-amine

HRID 2250404Notes

Reaction equation

HRID 2250404 reaction equation
[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5](Br)=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>O1CCOCC1>[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 1388782-Amino-5-bromo-3-nitropyridineHCID 2856454-Fluorophenylboronic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 219560765-(4-Fluorophenyl)-3-nitropyridin-2-amineYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

5.0 g of 2-amino-5-bromo-3-nitropyridine are dissolved in 120 ml of anoxic dioxane under a nitrogen atmosphere. Subsequently, 69 ml of an aqueous sodium bicarbonate solution (2.0 M), 5.4 g of 4-fluorophenyl-boronic acid, and 1.0 g of trans-dichloro-bis(tricyclohexylphosphane)palladium-(II) are added. The reaction mixture is refluxed at 110° C. for 17 hours. Thereafter, the volatile components are removed in vacuo and the remaining residue is redissolved in 2.0 l of a mixture of water/dichloromethane (1:1). The aqueous phase is extracted four times each with 625 ml of dichloromethane. The organic layer is separated, dried using sodium sulfate, and evaporated to dryness to yield a colorless, crude solid. Subsequently, the residue is purified by flash chromatography on silica gel (eluent: toluene/ethyl acetate 20:1) to afford 5.35 g of the title compound as a colorless solid of m.p. 232° C. MS: 234.2 (MH+). TLC: Rf=0.30 toluene/ethyl acetate 20:1).

Workup

  1. customThereafter, the volatile components are removed in vacuo
  2. dissolutionthe remaining residue is redissolved in 2.0 l of a mixture of water/dichloromethane (1:1)
  3. extractionThe aqueous phase is extracted four times each with 625 ml of dichloromethane
  4. customThe organic layer is separated
  5. customdried
  6. customevaporated to dryness
  7. customto yield a colorless, crude solid
  8. customSubsequently, the residue is purified by flash chromatography on silica gel (eluent: toluene/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-77fdf0d079e34427b3976c996c63fd2d
Source dataset
uspto-grants-2008_01
Patent number
US07317021B2

Reaction notes

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