Formaldehyde → 4-Fluoro-2-hydroxybenzaldehyde

HRID 575008Notes

Reaction equation

HRID 575008 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[Mg+2].[Cl-].[Cl-].[CH2:12]=[O:13]>CC#N>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:12]=[O:13])=[C:4]([OH:8])[CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 97433-FluorophenolHCID 5360315Magnesium Chloride

Product 1

HCID 27792684-Fluoro-2-hydroxybenzaldehydeYield 109%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
2.5 °C

Procedure

Into a 20-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 3-fluorophenol (400 g, 3.57 mol, 1.00 equiv) in CH3CN (5 L), followed by the addition of MgCl2 (1018 g, 3.00 equiv) in several batches at 0° C. To this was added TEA (1443 g, 14.26 mol, 4.00 equiv) dropwise with stirring at 0-5° C., followed by paraformaldehyde (640 g, 6.00 equiv). The resulting solution was stirred at 80° C. for 3 h, cooled to 20° C., quenched by the addition of 5 L of 2N HCl and extracted with 3×3 L of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 545 g (crude) of 4-fluoro-2-hydroxybenzaldehyde as a yellow solid.

Workup

  1. customInto a 20-L 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred at 80° C. for 3 h
  4. temperaturecooled to 20° C.
  5. customquenched by the addition of 5 L of 2N HCl
  6. extractionextracted with 3×3 L of ethyl acetate
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7cfac611897b4c53b14412e463557d73
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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