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

HRID 629638Notes

Reaction equation

HRID 629638 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 (3.0 g) in tetrahydrofuran (65 mL) was added potassium t-butoxide (1.979 g) portion wise. The resulting solution was stirred at ambient temperature for 30 minutes and a solution of 1,3-difluoro-2-nitrobenzene (2.338 g) in tetrahydrofuran (15 mL) was added dropwise. After 1 hour, the reaction was heated at reflux for 18 hours. The reaction was quenched with water (10 mL), diluted with brine (75 mL) and extracted with methylene chloride (2×75 mL). The crude product was isolated by concentration and purified on silica gel, eluted with a 10, 20, 50% ethyl acetate in hexane step gradient to provide the title compound.

Workup

  1. waitAfter 1 hour
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 18 hours
  4. customThe reaction was quenched with water (10 mL)
  5. additiondiluted with brine (75 mL)
  6. extractionextracted with methylene chloride (2×75 mL)
  7. customThe crude product was isolated by concentration
  8. custompurified on silica gel
  9. washeluted with a 10, 20, 50% ethyl acetate in hexane step gradient

Sources & evidence

ORD record
ord-5052b64015774f5099d9e3c6206609e1
Source dataset
uspto-grants-2016_04
Patent number
US09315488B2

Reaction notes

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