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

HRID 2273773Notes

Reaction equation

HRID 2273773 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-fd3c0821fee440e59b11252fb6d594b3
Source dataset
uspto-grants-2015_09
Patent number
US09125913B2

Reaction notes

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