Anisole → 2-Amino-4-nitropyridine

HRID 1640106Notes

Reaction equation

HRID 1640106 reaction equation
COC1C=CC(C[NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][N:10]=2)=CC=1.C1(OC)C=CC=CC=1>FC(F)(F)C(O)=O.[OH-].[Na+]>[NH2:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][N:10]=1

Participants

5

Reactant 2

HCID 7519AnisoleHCID 58902405N-(4-Methoxybenzyl)-4-nitropyridin-2-amine

Product 1

HCID 27628222-Amino-4-nitropyridineYield 67%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
80 °C

Procedure

N-(4-methoxybenzyl)-4-nitropyridin-2-amine (27.8 g, 0.11 mol) and anisole (13 mL, 0.12 mol) were dissolved in trifluoroacetic acid (112 mL) and heated at 80° C. for 2 h. The reaction mixture was allowed to cool to rt and concentrated. Trituration of the resulting residue with EtOAc and hexanes produced a light yellow solid that was isolated via filtration. The filtrate was allowed to stand overnight and a second crop of crystals was obtained. The combined batches of solids were dissolved in 1N NaOH (250 mL) and extracted with EtOAc (2×250 mL). The combined organic solutions were dried over MgSO4, filtered and concentrated to give 2-amino-4-nitropyridine as an orange solid (10.2 g, 67%). LCMS: (FA) ES+ 140.1.

Workup

  1. temperatureto cool to rt
  2. concentrationconcentrated
  3. customTrituration of the resulting residue with EtOAc and hexanes produced a light yellow solid
  4. customthat was isolated via filtration
  5. customa second crop of crystals was obtained
  6. extractionextracted with EtOAc (2×250 mL)
  7. dry with materialThe combined organic solutions were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ac4a13680c1840c69e2306eb57a4935b
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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