Hydrochloric Acid → 2-Fluoro-3-methoxybenzaldehyde

HRID 1869325Notes

Reaction equation

HRID 1869325 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[Li]C(CC)C.CN(C)[CH:17]=[O:18].Cl>O1CCCC1.C(OC)(C)(C)C>[F:1][C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][C:7]=1[CH:17]=[O:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 675762-FluoroanisoleHCID 178418400CID 53628100

Product 1

HCID 37744632-Fluoro-3-methoxybenzaldehydeYield 69.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-70 °C

Procedure

27 ml (240.62 mmol) of 2-fluoroanisole is dissolved in 700 ml of tetrahydrofuran. At −70° C., 200 ml of sec-BuLi (1.3 M solution in cyclohexane) is added in drops. It is stirred for one hour at −70° C., and then 152 ml of N,N-dimethylformamide, dissolved in 50 ml of tetrahydrofuran, is added in drops at this temperature. After another hour of stirring at −70° C., 380 ml of hydrochloric acid (w=10%) is added in drops. In this case, the batch slowly comes to room temperature. After stirring overnight at room temperature, methyl tert-butyl ether is added, and the organic phase is separated after vigorous stirring. The aqueous phase is extracted two more times with methyl tert-butyl ether. The combined organic extracts are washed with brine and dried. After the desiccant is filtered off, the solvent is spun off, and the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 25.66 g (69.2%) of the desired compound is isolated.

Workup

  1. additionis added in drops at this temperature
  2. stirringAfter another hour of stirring at −70° C.
  3. customslowly comes to room temperature
  4. stirringAfter stirring overnight at room temperature
  5. customthe organic phase is separated after vigorous stirring
  6. extractionThe aqueous phase is extracted two more times with methyl tert-butyl ether
  7. washThe combined organic extracts are washed with brine
  8. customdried
  9. filtrationAfter the desiccant is filtered off
  10. customthe residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

Sources & evidence

ORD record
ord-1e74175faaac407f9914e6d4de20a4a6
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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