Hydrochloric Acid → 8-Fluoro-2,3-dihydro-4H-1-benzopyran-4-one

HRID 1887428Notes

Reaction equation

HRID 1887428 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[H-].[Na+].Br[CH2:12][CH2:13][C:14](O)=[O:15].Cl>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[O:8][CH2:12][CH2:13][C:14]2=[O:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 97072-Fluorophenol2×HCID 115533-Bromopropionic acidHCID 24758Sodium hydride

Product 1

HCID 139538178-Fluoro-2,3-dihydro-4H-1-benzopyran-4-oneYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 2-fluorophenol (Compound 1-1, 3.0 g) in N,N-dimethylformamide (7.0 ml) was added to a solution of 50% sodium hydride (3.22 g) in N,N-dimethylformamide (100 ml) in a nitrogen atmosphere with cooling in an ice bath. After stirring at the same temperature for 30 minutes, a solution of 3-bromo-propionic acid (4.91 g) in N,N-dimethylformamide (8.0 ml) was added. The mixture was returned to room temperature and stirred at the same temperature for 24 hours. The pH was adjusted to 1 to 2 with 1 N hydrochloric acid (100 ml) to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized by adding a mixed solvent of 20% ethyl acetate-hexane to obtain the title compound (1.53 g). (1-2) The title compound was synthesized by the following alternative method.

Workup

  1. temperaturewith cooling in an ice bath
  2. customwas returned to room temperature
  3. stirringstirred at the same temperature for 24 hours
  4. customto terminate
  5. customthe reaction
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washthe organic layer was washed with brine
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was crystallized
  11. additionby adding a mixed solvent of 20% ethyl acetate-hexane

Sources & evidence

ORD record
ord-3e66de65c3e34837ac8abc4e0c245897
Source dataset
uspto-grants-2013_08
Patent number
US08501733B2

Reaction notes

Loading…