Hydrochloric Acid → HCID 19094453, compound

HRID 2248296Notes

Reaction equation

HRID 2248296 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[H-].[Na+].[C:14](OCC)(=O)[CH2:15][CH2:16][CH3:17].Cl>O1CCCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[O:1][C:14]([CH2:15][CH2:16][CH3:17])=[CH:10][C:9](=[O:11])[C:3]=2[CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7762Ethyl butyrateHCID 24758Sodium hydrideHCID 959922-Acetyl-4-fluorophenol

Product 1

HCID 19094453HCID 19094453, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2'-hydroxy-5'-fluoroacetophenone (2 gm) in tetrahydrofuran (10 mL) was added dropwise to sodium hydride (600 mg), then ethyl butyrate (10 mL) was added. After 30 minutes, aqueous 1N HCl (50 mL) was added, and the mixture extracted with ethyl acetate, and the extracts washed with H2O, saturated aqueous NaHCO3, brine, dried (Na2SO4), filtered and evaporated. The residue was dissolved in dichloromethane (100 mL), and trifluoroacetic acid (7 mL) added, and after stirring overnight at room temperature, dichloromethane and saturated aqueous NaHCO3 were added, and the layers separated. The organic layer was washed with H2O, brine, dried (Na2SO4), filtered and concentrated in vacuo to yield 6-fluoro-2-propyl-4H-1-benzopyran-4-one (2.4 gm, Rf=0.4 1:1 diethyl ether/hexanes). This compound (9 gm) was dissolved in ethanol (250 mL) and sodium borohydride (1.6 gm) added, and the mixture heated under reflux. After 3.5 hours additional sodium borohydride (1.6 gm) added, and after 7 hours a further addition of sodium borohydride (1.6 gm) was made. After 10 hours more sodium borohydride (0.8 gm) was added and after 23 hours total reaction time the mixture was concentrated under reduced pressure, and partitioned between ethyl acetate and H2O. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated to yield 4-hydroxy-2,3-dihydro-6-fluoro-2-propyl-4H-1-benzopyran-4-one (Rf=0.4 1:1 diethyl ether/hexanes). This material (10.8 gm) was dissolved in acetic acid (45 mL) and a solution of chromium trioxide (7.8 gm) in acetic acid (45 mL)/H2O (10 mL) was added dropwise. After one hour, the mixture was poured into ice/H2O (1L) and extracted with ethyl acetate. The extracts were washed with H2O, saturated NaHCO3, dried (Na2SO4), filtered and evaporated to yield the title compound (7.4 g, Rf=0.7, 1:1 diethyl ether/hexanes).

Workup

  1. extractionthe mixture extracted with ethyl acetate
  2. washthe extracts washed with H2O, saturated aqueous NaHCO3, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  7. additiontrifluoroacetic acid (7 mL) added
  8. additiondichloromethane and saturated aqueous NaHCO3 were added
  9. customthe layers separated
  10. washThe organic layer was washed with H2O, brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fab3269dcb184244befcc0f0b064a83c
Source dataset
uspto-grants-1991_08
Patent number
US05039672

Reaction notes

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