1,3-Difluoro-2-nitrobenzene → Methyl 4-fluoro-2-(3-fluoro-2-nitrophenoxy)benzoate

HRID 624433Notes

Reaction equation

HRID 624433 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([OH:12])[CH:3]=1.CC(C)([O-])C.[K+].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](F)[C:21]=1[N+:27]([O-:29])=[O:28]>O1CCCC1>[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([F:19])[C:21]=2[N+:27]([O-:29])=[O:28])[CH:3]=1

Participants

5

Reactant 3

HCID 879221,3-Difluoro-2-nitrobenzeneHCID 2775386Methyl 4-fluorosalicylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 67227494Methyl 4-fluoro-2-(3-fluoro-2-nitrophenoxy)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl 4-fluoro-2-hydroxybenzoate (1.225 g) in anhydrous tetrahydrofuran (25 mL) was added potassium t-butoxide (0.808 g). The mixture was stirred for 20 minutes at room temperature. A solution of 1,3-difluoro-2-nitrobenzene (0.955 g) in tetrahydrofuran (6 mL) was then added dropwise. The resulting mixture was stirred at room temperature for 1 hour, then at 80° C. overnight. The reaction mixture was quenched with water (40 mL) and extracted with dichloromethane. The organic solution was dried (MgSO4), filtered and concentrated. The residue was purified on a silica gel column, eluting with 25% ethyl acetate in hexane to obtain the title compound.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 hour
  2. customat 80° C.
  3. customovernight
  4. customThe reaction mixture was quenched with water (40 mL)
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic solution was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on a silica gel column
  10. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e3fcd0a75b7042bcab1bef822f03dd5d
Source dataset
uspto-grants-2016_04
Patent number
US09303025B2

Reaction notes

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