Hydrochloric Acid → 2-Fluorobenzofuran-5-carbaldehyde

HRID 45627Notes

Reaction equation

HRID 45627 reaction equation
[Mg].II.Br[C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([F:13])=[CH:10][C:9]=2[CH:14]=1.Cl.[O:16]1CCC[CH2:17]1>[Cl-].[Na+].O.CN(C)C=O>[F:13][C:11]1[O:12][C:8]2[CH:7]=[CH:6][C:5]([CH:17]=[O:16])=[CH:14][C:9]=2[CH:10]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 807IodineHCID 8028Tetrahydrofuran2×HCID 5462224MagnesiumHCID 574391135-Bromo-2-fluoro-1-benzofuran

Product 1

HCID 450908312-Fluorobenzofuran-5-carbaldehyde

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A slurry of magnesium powder (219 mg) and iodine (cat) in dry tetrahydrofuran (3 ml) was heated at 50° C. under nitrogen for 20 minutes. 5-Bromo-2-fluoro-1-benzofuran (1.4 g) was dissolved in dry tetrahydrofuran (6 ml). A 1 ml portion of the solution was added to the slurry at 50° C. without stirring. After 30 minutes the rest of the solution was added slowly and the reaction was heated at reflux for 3 hours. The reaction was cooled in an ice/water bath and dimethylformamide (1 ml) was added dropwise maintaining the temperature below 10° C. After 1 hour a mixture of 2N hydrochloric acid (12.5 ml) and brine (12.5 ml) was added. The reaction mixture was extracted using ethyl acetate (3×25 ml). The combined organics were washed with brine and dried over anhydrous magnesium sulphate. The solvent was removed in vacuo and the residue applied to a silica cartridge (50 g). This was eluted with cyclohexane, cyclohexane/ethyl acetate (6:1, 5:1 v/v). This gave 2-fluoro-5-formyl-1-benzofuran (376 mg).

Workup

  1. additionA 1 ml portion of the solution was added to the slurry at 50° C.
  2. additionAfter 30 minutes the rest of the solution was added slowly
  3. temperaturethe reaction was heated
  4. temperatureat reflux for 3 hours
  5. temperatureThe reaction was cooled in an ice/water bath
  6. temperaturemaintaining the temperature below 10° C
  7. additionwas added
  8. extractionThe reaction mixture was extracted
  9. washThe combined organics were washed with brine
  10. dry with materialdried over anhydrous magnesium sulphate
  11. customThe solvent was removed in vacuo
  12. washThis was eluted with cyclohexane, cyclohexane/ethyl acetate (6:1, 5:1 v/v)

Sources & evidence

ORD record
ord-f85faedff01e4a4cbbd3deb2185f6973
Source dataset
uspto-grants-2013_09
Patent number
US08541579B2

Reaction notes

Loading…