2-Methyl-5-hydroxypyridine → 2-Methyl-5-(2-methyl-4-nitrophenoxy)pyridine

HRID 1864329Notes

Reaction equation

HRID 1864329 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[CH:6][C:7]([CH3:10])=[N:8][CH:9]=1.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21]>CC(N(C)C)=O>[CH3:10][C:7]1[CH:6]=[CH:5][C:4]([O:3][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=2[CH3:21])=[CH:9][N:8]=1

Participants

5

Reactant 3

HCID 142752-Methyl-5-hydroxypyridineHCID 24758Sodium hydrideHCID 68001Benzene, 1-fluoro-2-methyl-4-nitro-

Product 1

HCID 179901022-Methyl-5-(2-methyl-4-nitrophenoxy)pyridineYield 98%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

Sodium hydride (25.6 g, 60% dispersion in oil, 0.64 mol) was added portion wise to a solution of 5-hydroxy-2-methylpyridine (70 g, 0.64 mol) in DMA (700 ml) while keeping the temperature below 40° C. At the end of the addition, the mixture was stirred at room temperature for 1 hour and 2-fluoro-5-nitrotoluene (91.3 g, 0.59 mol) in DMA (100 ml) was added slowly. The mixture was stirred at 80° C. for 3 hours and then cooled. The solvents were evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer washed with water and brine, dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 30% ethyl acetate in petroleum ether) to give 2-methyl-5-(2-methyl-4-nitrophenoxy)pyridine (141 g, 98%) as an oil; NMR spectrum (CDCl3); 2.43 (s, 3H), 2.59 (s, 3H), 6.74 (d, 1H), 7.21 (d, 1H), 7.27 (d, 1H), 8.00 (d, 1H), 8.17 (s, 1H), 8.32 (s, 1H).

Workup

  1. customthe temperature below 40° C
  2. additionAt the end of the addition
  3. stirringThe mixture was stirred at 80° C. for 3 hours
  4. temperaturecooled
  5. customThe solvents were evaporated under vacuum
  6. customthe residue was partitioned between ethyl acetate and water
  7. washThe organic layer washed with water and brine
  8. dry with materialdried over MgSO4
  9. customAfter evaporation of the solvents
  10. customthe residue was purified by chromatography on silica gel (eluant: 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-7a9ae051f75540908136f28057a50910
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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