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

HRID 1672635Notes

Reaction equation

HRID 1672635 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.C(Cl)Cl>[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)phenolYield 79.5%

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 introduced into 500 ml of dry THF and cooled to 0° C. Then, while cooling, 238 ml (238 mmol) of a 1 M solution of lithium aluminum hydride in THF are slowly added dropwise, and the mixture is stirred at 0° C. for 1 hour and then at RT overnight. After reaction is complete, the mixture is mixed with saturated ammonium chloride solution and taken up in methylene chloride, and the organic phase is separated off and dried over sodium sulfate. After filtration, the solvent is removed in vacuo. The crude product is purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1). 18.0 g (126.6 mmol, 79% yield) of a colorless solid are isolated.

Workup

  1. temperatureThen, while cooling
  2. customat RT
  3. customovernight
  4. customAfter reaction
  5. customthe organic phase is separated off
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent is removed in vacuo
  9. customThe crude product is purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-00ed318f4a7f4a19bc706c93ecb1daf0
Source dataset
uspto-grants-2011_08
Patent number
US07998988B2

Reaction notes

Loading…