N-[4-(benzyloxy)phenyl]-4-methyl-3-nitropyridin-2-amine → N2-[4-(benzyloxy)phenyl]-4-methylpyridine-2,3-diamine

HRID 82631Notes

Reaction equation

HRID 82631 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([N+:22]([O-])=O)=[C:20]([CH3:25])[CH:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1.C(O)(=O)C.O.[Zn]>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([NH2:22])=[C:20]([CH3:25])[CH:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 1

HCID 58577297N-[4-(benzyloxy)phenyl]-4-methyl-3-nitropyridin-2-amine

Product 1

HCID 58577506N2-[4-(benzyloxy)phenyl]-4-methylpyridine-2,3-diamineYield 97.4%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[4-(benzyloxy)phenyl]-4-methyl-3-nitropyridin-2-amine (154.5 g) in THF (1300 mL), acetic acid (260 mL) and water (13 mL) was slowly added zinc powder (300 g) over 35 min. After zinc was added, the mixture was stirred at room temperature for 1 h. The reaction mixture was filtered through celite, and insoluble materials were washed with THF (3 L). The filtrate was combined and concentrated. To the residue were added EtOAc (1.2 L) and 2.5 N NaOH (1.2 L) under ice cooling, and then the mixture was stirred at room temperature for 30 min. The mixture was filtered through celite, and insoluble materials were washed with EtOAc (3 L). The organic layer was separated, washed with water (300 mL) and brine (300 mL×2), dried over MgSO4 and concentrated to give a crude N2-[4-(benzyloxy)phenyl]-4-methylpyridine-2,3-diamine (137 g) as black oil. This product was subjected to the next reaction without further purification.

Workup

  1. customover 35 min
  2. filtrationThe reaction mixture was filtered through celite, and insoluble materials
  3. washwere washed with THF (3 L)
  4. concentrationconcentrated
  5. additionTo the residue were added EtOAc (1.2 L) and 2.5 N NaOH (1.2 L) under ice cooling
  6. stirringthe mixture was stirred at room temperature for 30 min
  7. filtrationThe mixture was filtered through celite, and insoluble materials
  8. washwere washed with EtOAc (3 L)
  9. customThe organic layer was separated
  10. washwashed with water (300 mL) and brine (300 mL×2)
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-27003454e7b747e0a75500212e459eec
Source dataset
uspto-grants-2014_09
Patent number
US08846713B2

Reaction notes

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