Anisole → 2-Amino-4-nitropyridine
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+]>[N+:15]([C:13]1[CH:12]=[CH:11][N:10]=[C:9]([NH2:8])[CH:14]=1)([O-:17])=[O:16]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 80 °C
Procedure
N-(4-methoxybenzyl)-4-nitropyridin-2-amine (Int-21, 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 magnesium sulfate, filtered and concentrated to give 4-nitropyridin-2-amine as an orange solid (10.2 g, 67%). LCMS: (FA) ES+ 140; 1H NMR (400 MHz, CD3OD) δ ppm 8.15 (dd, J=5.7, 0.6 Hz, 1H), 7.23 (dd, J=2.0, 0.6 Hz, 1H), 7.20 (dd, J=5.7, 2.0 Hz, 1H).
Workup
- temperatureto cool to rt
- concentrationconcentrated
- customTrituration of the resulting residue with EtOAc and hexanes produced a light yellow solid
- customthat was isolated via filtration
- customa second crop of crystals was obtained
- extractionextracted with EtOAc (2×250 mL)
- dry with materialThe combined organic solutions were dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-ddb2a9513e694e548e4856b23c2a3a42
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08513421B2
Reaction notes
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