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

HRID 573158Notes

Reaction equation

HRID 573158 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-d9073d7030874f248998c733b01aa736
Source dataset
uspto-grants-2015_05
Patent number
US09029404B2

Reaction notes

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