Ethyl Acetate → tert-Butyl 2-fluoro-4-formylbenzoate

HRID 589937Notes

Reaction equation

HRID 589937 reaction equation
N[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([F:15])[C:3]=1C=NO.[C:19](OCC)(=[O:21])C>C(O)C.C(O)(=O)C.[Ni]>[F:15][C:4]1[CH:3]=[C:2]([CH:19]=[O:21])[CH:14]=[CH:13][C:5]=1[C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7]

Participants

6

Reactant 2

HCID 8857Ethyl AcetateHCID 131734471tert-Butyl 4-amino(hydroxyimino)methyl-2-fluorobenzoate

Product 1

HCID 86607392tert-Butyl 2-fluoro-4-formylbenzoateYield 56%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

tert-Butyl 4-amino(hydroxyimino)methyl-2-fluorobenzoate (WO 2011/016469) (3.90 g, 17.6 mmol) was dissolved in ethanol (40 mL) and acetic acid (40 mL). Raney nickel (ca. 10 g) was added to the mixture at room temperature, and the resulting mixture was stirred for 1 hour under hydrogen flow. After the insoluble material was removed by filtration through Celite, water was added to the filtrate, and the resulting mixture was extracted three times with ethyl acetate, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then water and a saturated aqueous solution of sodium hydrogen carbonate were added to the mixture. The resulting mixture was extracted with ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→2:1, v/v) to give the title compound (2.21 g, yield: 56%).

Workup

  1. customAfter the insoluble material was removed by filtration through Celite, water
  2. additionwas added to the filtrate
  3. extractionthe resulting mixture was extracted three times with ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. additionwater and a saturated aqueous solution of sodium hydrogen carbonate were added to the mixture
  7. extractionThe resulting mixture was extracted with ethyl acetate
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-147c4ea4c4e84dc086d7975aa4b0c0ec
Source dataset
uspto-grants-2016_01
Patent number
US09233958B2

Reaction notes

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