Hydrochloric Acid → Ethyl 7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2h-1-benzopyran-3-carboxylate

HRID 722283Notes

Reaction equation

HRID 722283 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([OH:13])[C:8](=[CH:11][CH:12]=1)[CH:9]=O)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:20][C:21]([F:30])([F:29])/[CH:22]=[CH:23]/[C:24]([O:26][CH2:27][CH3:28])=[O:25].Cl>CN(C)C=O.C(O)C.O.CCCCCC.C(OCC)(=O)C>[CH3:2][C:1]([C:5]1[CH:12]=[CH:11][C:8]2[CH:9]=[C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:22]([C:21]([F:20])([F:30])[F:29])[O:13][C:7]=2[CH:6]=1)([CH3:4])[CH3:3]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoateHCID 137652724-tert-Butyl-2-hydroxybenzaldehyde

Product 1

HCID 21883685Ethyl 7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2h-1-benzopyran-3-carboxylateYield 71.4%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A one liter three-neck flask was charged with 4-tert-butylsalicylaldehyde (Step 1) (100.0 g, 0.56 mole), dimethylformamide (110 mL), and potassium carbonate (79.9 g, 0.58 mole) causing the temperature of the mixture to rise to 40° C. Ethyl 4,4,4-trifluorocrotonate (118.0 g, 0.70 mole) in dimethylformamide (110 mL) was added and the mixture heated to 60° C. at which time the reaction temperature rose to 70° C. The reaction was cooled to 60° C., maintained at 60° C. (with added heating) for 8.5 hours and cooled to room temperature. Ethyl acetate (600 mL) and 3 N HCl (600 mL) were added, mixed, and the layers separated. The aqueous phase was extracted with ethyl acetate and the organic phases were combined. The combined organic phases were washed with brine-water (1:1), brine, dried over MgSO4, filtered and concentrated in vacuo, yielding a semi-solid. Hexane (600 mL) was added with mixing and the mixture was filtered. The filtrate was washed with brine, dried over MgSO4, filtered and concentrated in vacua yielding a solid. This solid was dissolved in hot ethanol (600 mL). Water (190 mL) was added which induced crystallization. Filtration of the mixture and drying of the product provided the desired ester as a crystalline solid (131.3 g, 71%): mp 91.0–94.9° C. This material was of suitable purity to be used in subsequent steps without further purification.

Workup

  1. customto rise to 40° C
  2. customrose to 70° C
  3. temperatureThe reaction was cooled to 60° C.
  4. temperaturemaintained at 60° C.
  5. addition(with added heating) for 8.5 hours
  6. temperaturecooled to room temperature
  7. additionmixed
  8. customthe layers separated
  9. extractionThe aqueous phase was extracted with ethyl acetate
  10. washThe combined organic phases were washed with brine-water (1:1), brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customyielding a semi-solid
  15. additionwith mixing
  16. filtrationthe mixture was filtered
  17. washThe filtrate was washed with brine
  18. dry with materialdried over MgSO4
  19. filtrationfiltered
  20. concentrationconcentrated in vacua
  21. customyielding a solid
  22. customcrystallization
  23. filtrationFiltration of the mixture
  24. customdrying of the product

Sources & evidence

ORD record
ord-73298fe0ce344c34924519f6d2ec89d7
Source dataset
uspto-grants-2006_11
Patent number
US07138411B2

Reaction notes

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