2-Aminopyridine → (5-Fluoro-2-nitrophenyl)pyridin-2-yl-amine

HRID 243005Notes

Reaction equation

HRID 243005 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.F[C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[N+:18]([O-:20])=[O:19]>C1COCC1>[F:17][C:15]1[CH:14]=[CH:13][C:12]([N+:18]([O-:20])=[O:19])=[C:11]([NH:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=2)[CH:16]=1

Participants

5

Reactant 3

HCID 104392-AminopyridineHCID 24758Sodium hydrideHCID 679672,4-Difluoronitrobenzene

Product 1

HCID 68157116(5-Fluoro-2-nitrophenyl)pyridin-2-yl-amineYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Prep 2: Sodium hydride (48.6 g, 60% by wt, 1.22 mol) was added piecewise to a solution of 2-aminopyridine (57.2 g, 0.61 mol) in THF (400 mL) at 0° C. at such a rate that T≦18° C. The reaction mixture was stirred at 0° C. for 10 min. then added via cannula to a solution of 2,4-difluoronitrobenzene in THF (350 mL) at −20° C. at such a rate that T≦10° C. The reaction was stirred at −40° C. for 1 h then allowed to warm to RT. As the reaction reached RT the temperature rose rapidly to 35° C. and effervescence was observed. The reaction mixture was poured onto ice (˜2 L) and the solid which formed collected by filtration. The solid was washed with pentane and dried in vacuo to give the (5-fluoro-2-nitrophenyl)pyridin-2-yl-amine as a bright orange solid (139.3 g, 94%).

Workup

  1. stirringThe reaction was stirred at −40° C. for 1 h
  2. temperatureto warm to RT
  3. customreached RT
  4. customrose rapidly to 35° C.
  5. additionThe reaction mixture was poured onto ice (˜2 L)
  6. customthe solid which formed
  7. filtrationcollected by filtration
  8. washThe solid was washed with pentane
  9. customdried in vacuo

Sources & evidence

ORD record
ord-677934be1f4a4b38bb98cc9b97f7d3fa
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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