Hydrochloric Acid → 4-Fluoro-2-methylbenzaldehyde

HRID 1822281Notes

Reaction equation

HRID 1822281 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH3:9].C([Li])CCC.CN([CH:18]=[O:19])C.Cl>C1COCC1.CCOCC>[F:8][C:5]1[CH:6]=[CH:7][C:2]([CH:18]=[O:19])=[C:3]([CH3:9])[CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 967432-Bromo-5-fluorotolueneHCID 178418339Butyllithium

Product 1

HCID 27832174-Fluoro-2-methylbenzaldehydeYield 71.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of 2-bromo-5-fluorotoluene (12.0 g, 63.5 mmol) in dry THF (60 mL) is treated with a 1.6 M hexanes solution of n-butyl lithium (59.5 mL, 95.3 mmol) and then stirred for 15 minutes at −78° C. under N2. The mixture is then treated with DMF (27.8 g, 0.381 mol) and warmed to rt. The reaction is acidified with 1 N HCl, diluted with Et2O and extracted with water. The organic layer is dried (Na2SO4), and the solvent removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using a gradient of 5/1 to 3/1 to hexanes/ethyl acetate to afford 6.24 g (71%) of the title compound. Rf=0.49 (2/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3).

Workup

  1. temperaturewarmed to rt
  2. extractionextracted with water
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. customthe solvent removed in vacuo
  5. customto afford crude product that
  6. customis absorbed on silica gel
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-241ac859313842d3ba170025b55e3b46
Source dataset
uspto-grants-2009_10
Patent number
US07608639B2

Reaction notes

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