3-Hydroxypyridine → 2-Nitro-5-(pyridin-3-yloxy)-4-trifluoromethyl-benzoic acid methyl ester

HRID 2069274Notes

Reaction equation

HRID 2069274 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.[CH3:10][O:11][C:12](=[O:27])[C:13]1[CH:18]=[C:17](F)[C:16]([C:20]([F:23])([F:22])[F:21])=[CH:15][C:14]=1[N+:24]([O-:26])=[O:25].C(OCC)(=O)C.C1CCCCC1>O1CCCC1.O>[CH3:10][O:11][C:12](=[O:27])[C:13]1[CH:18]=[C:17]([O:3][C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[C:16]([C:20]([F:23])([F:22])[F:21])=[CH:15][C:14]=1[N+:24]([O-:26])=[O:25]

Participants

7

Reactant 4

HCID 79713-HydroxypyridineHCID 24758Sodium hydrideHCID 21867204Cyclohexane ethylacetateHCID 589644905-Fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 589644842-Nitro-5-(pyridin-3-yloxy)-4-trifluoromethyl-benzoic acid methyl esterYield 76.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of 198 mg (4.53 mmol) of sodium hydride (65% in oil, washed with pentane) in 2.5 ml of dry tetrahydrofuran a solution of 356 mg (3.74 mmol) of 3-hydroxypyridine in 5 ml of tetrahydrofuran is dropped and the mixture stirred for 1 hour at room temperature. After cooling to 0° C. 1.0 g (3.74 mmol) of 5-fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester dissolved in 10 ml of tetrahydrofuran is added and stirring continued for 7 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with brine, dried over Na2SO4 and evaporated to give an oil which is fractionated by medium pressure chromatography on silica with ethyl acetate/cyclohexane 1:1. The fractions containing the product are combined and evaporated yielding 977 mg of 2-nitro-5-(pyridin-3-yloxy)-4-trifluoromethyl-benzoic acid methyl ester as white powder, m.p. 98-100° C.

Workup

  1. additionis dropped
  2. temperatureAfter cooling to 0° C
  3. additionis added
  4. stirringstirring
  5. waitcontinued for 7 hours
  6. extractionextracted with ethyl acetate
  7. washThe organic phase is washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customto give an oil which
  11. additionThe fractions containing the product
  12. customevaporated

Sources & evidence

ORD record
ord-9a5da3147a8d4f61a1b76a9ab1d6e291
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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