Oxygen → 4-Fluoro-2-(hydroxymethyl)phenol

HRID 1512194Notes

Reaction equation

HRID 1512194 reaction equation
O=O.[F:3][C:4]1[CH:5]=[CH:6][C:7]([OH:14])=[C:8]([CH:13]=1)[C:9](OC)=[O:10].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+]>C1COCC1.ClCCl>[F:3][C:4]1[CH:5]=[CH:6][C:7]([OH:14])=[C:8]([CH2:9][OH:10])[CH:13]=1

Participants

7

Reactant 4

HCID 977OxygenHCID 25517Ammonium ChlorideHCID 2783186Methyl 5-fluoro-2-hydroxybenzoateHCID 21226445Aluminium lithium hydride

Product 1

HCID 106068384-Fluoro-2-(hydroxymethyl)phenol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

With exclusion of oxygen, 27.1 g (159.28 mmol) of methyl 5-fluoro-2-hydroxybenzoate are initially charged in 500 ml of dry THF and cooled to 0° C. With cooling, 238 ml (238 mmol) of a 1 M solution of lithium aluminum hydride in THF are then slowly added dropwise, and the mixture is stirred at 0° C. for 1 hour and then at RT overnight. After the reaction has gone to completion, saturated ammonium chloride solution is added, and the mixture is taken up in dichloromethane. The organic phase is separated off and dried over sodium sulfate. After filtration, the solvent is removed under reduced pressure. The crude product is purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1). This gives 18.0 g (126.6 mmol, 79% of theory) of a colorless solid.

Workup

  1. temperatureWith cooling
  2. customat RT
  3. customovernight
  4. additionis added
  5. customThe organic phase is separated off
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent is removed under reduced pressure
  9. customThe crude product is purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-fe249ccc93d3492fa5d51f0979291677
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

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