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

HRID 415002

Reaction equation

HRID 415002 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21]>CN(C=O)C>[CH3:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=2[CH3:21])=[CH:8][N:9]=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 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 500 mL flask equipped with addition funnel at 0° C. was added NaH (8.26 g, 95%, 327 mmol), followed by slow addition of DMF (100 mL). The mixture was stirred for 10 minutes. The addition funnel was then charged with 6-methyl-pyridin-3-ol (30.2 g, 277 mmol) and DMF (100 mL), and the solution in addition funnel was added to the flask dropwise over 45 minutes. The reaction mixture was stirred at 0° C. for another 30 minutes once the addition was finished. To the addition funnel was then added 4-fluoro-3-methyl-nitrobenzene (39.1 g, 252 mmol) and DMF (100 mL) and the resulting solution was added to the flask dropwise over 45 minutes. The cold bath was removed at the end of the addition and the reaction mixture was allowed to stir at room temperature for 15 hours. The red dark solution was cooled to 0° C. and water (100 mL) was added cautiously to the reaction mixture. The resulting solution was stirred for 30 minutes and solid product was purified by filtration and washed with cold water (500 mL). The wet solid was dried in vacuo to give product (49.8 g, 81%).

Workup

  1. customTo a 500 mL flask equipped with addition funnel at 0° C.
  2. additionthe solution in addition funnel
  3. additionwas added to the flask dropwise over 45 minutes
  4. stirringThe reaction mixture was stirred at 0° C. for another 30 minutes once the addition
  5. customThe cold bath was removed at the end of the addition
  6. stirringto stir at room temperature for 15 hours
  7. additionwater (100 mL) was added cautiously to the reaction mixture
  8. stirringThe resulting solution was stirred for 30 minutes
  9. filtrationsolid product was purified by filtration
  10. washwashed with cold water (500 mL)
  11. customThe wet solid was dried in vacuo

Sources & evidence

ORD record
ord-a4a62c22ffd64f01949204ec3778899b
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Linked notes

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