Hydrochloric Acid → 4-(4-fluorophenyl)dihydro-2H-pyran-2,6(3H)-dione

HRID 1402803Notes

Reaction equation

HRID 1402803 reaction equation
FC1C=CC(C=O)=CC=1.[OH-].[Na+].Cl.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([CH2:25][C:26]([OH:28])=[O:27])[CH2:21][C:22]([OH:24])=O)=[CH:16][CH:15]=1>C(OCC)(=O)CC(C)=O.C(Cl)(=O)C.C(O)C>[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH:20]2[CH2:21][C:22](=[O:24])[O:28][C:26](=[O:27])[CH2:25]2)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 680234-FluorobenzaldehydeHCID 769903-(4-Fluorophenyl)pentanedioic acid

Product 1

HCID 111600754-(4-fluorophenyl)dihydro-2H-pyran-2,6(3H)-dione

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6367Acetyl chlorideSolventHCID 8868Ethyl AcetoacetateSolvent

Procedure

To a solution of commercial 4-fluorobenzaldehyde (12.4 g) in ethyl acetoacetate (25.3 ml) piperidine (2 ml) was added with stirring at rt. The cloudy solution solidifies within 3 h. The yellow solid was crushed, slurried with ethanol (20 ml), collected by suction filtration, and washed with ethanol. After drying in vacuo 27 g of a faint yellowish solid (the bis-adduct of acetoacetate to the benzaldehyde) was isolated. The powdered solid was added in portions to 40% NaOH (400 g) with stirring. The resulting yellow slurry was stirred at reflux for 2 h. After cooling in an ice bath the mixture was acidified by portionwise addition of conc. HCl (370 ml) to give a colourless precipitate. The solid was collected by suction filtration and washed with water. After drying in vacuo 3-(4-fluorophenyl)glutaric acid (12.3 g) was obtained. The suspension of finely divided 3-(4-fluorophenyl)glutaric acid in acetyl chloride (20 ml) was heated to reflux with stirring for 1 h. After cooling to rt precipitation of the product is completed by addition of petrol ether (150 ml). The precipitate is isolated by suction filtration, washed with petrol ether, and dried in vacuo to give 3-(4-fluorophenyl)glutaric anhydride (9.4 g) as colourless crystals.

Workup

  1. customThe yellow solid was crushed
  2. filtrationcollected by suction filtration
  3. washwashed with ethanol
  4. dry with materialAfter drying in vacuo 27 g of a faint yellowish solid (the bis-adduct of acetoacetate to the benzaldehyde)
  5. customwas isolated
  6. stirringwith stirring
  7. stirringThe resulting yellow slurry was stirred
  8. temperatureat reflux for 2 h
  9. temperatureAfter cooling in an ice bath the mixture
  10. customto give a colourless precipitate
  11. filtrationThe solid was collected by suction filtration
  12. washwashed with water
  13. dry with materialAfter drying in vacuo 3-(4-fluorophenyl)glutaric acid (12.3 g)
  14. customwas obtained
  15. temperaturewas heated
  16. temperatureto reflux
  17. stirringwith stirring for 1 h
  18. temperatureAfter cooling to rt
  19. customprecipitation of the product
  20. additionis completed by addition of petrol ether (150 ml)
  21. customThe precipitate is isolated by suction filtration
  22. washwashed with petrol ether
  23. customdried in vacuo

Sources & evidence

ORD record
ord-f8e3a69fb8634f86aabe1cd2bc90f9e2
Source dataset
uspto-grants-2014_12
Patent number
US08912186B2

Reaction notes

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