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

HRID 1750750Notes

Reaction equation

HRID 1750750 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) portionwise. 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 twice methylene chloride (75 ml). The crude product was isolated by concentration and purified on silica gel, and eluted with a 10, 20, 50% ethyl acetate in hexane step gradient.

Workup

  1. temperatureAfter 1 hour the reaction was heated
  2. temperatureat reflux for 18 hours
  3. customThe reaction was quenched with water (10 ml)
  4. additiondiluted with brine (75 ml)
  5. extractionextracted with twice methylene chloride (75 ml)

Sources & evidence

ORD record
ord-3cd5e688512242898adb1600df445de2
Source dataset
uspto-grants-2015_10
Patent number
US09156856B2

Reaction notes

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