Potassium Carbonate → ethyl 6-formyl-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate

HRID 2214858Notes

Reaction equation

HRID 2214858 reaction equation
[CH:1]([C:3]1[CH:10]=[C:7]([CH:8]=O)[C:6]([OH:11])=[CH:5][CH:4]=1)=[O:2].[F:12][C:13]([F:22])([F:21])/[CH:14]=[CH:15]/[C:16]([O:18][CH2:19][CH3:20])=[O:17].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:14]([C:13]([F:12])([F:22])[F:21])[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:8][C:7]=2[CH:10]=1)=[O:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1651064-HydroxyisophthalaldehydeHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate2×

Product 1

HCID 21883688ethyl 6-formyl-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A 50 mL round bottom flask was charged with 5-formylsalicylaldehyde (3.21 g, 21.39 mmol), ethyl 4,4,4-trifluorocrotonate (3.50 mL, 3.96 g, 23.53 mmol), dimethylformamide (15 mL) and potassium carbonate (2.95 g, 21.39 mmol) and heated to 60° C. for 12 hours. Additional ethyl 4,4,4-trifluorocrotonate (3.50 mL, 3.96 g, 23.53 mmol) was added and the reaction heated for 16 hours at 75° C. After cooling to room temperature, the reaction was partitioned between H2O and diethyl ether. The organic phase was washed with saturated NaHCO3 solution, KHSO4 solution (0.25 M), brine, treated with decolorizing carbon (warmed gently). The resulting black suspension was dried over MgSO4, vacuum filtered through diatomaceous earth, and concentrated in vacuo yielding an orange crystalline mass. This material was recrystallized from hot hexanes yielding the ester (1.51 g, 24%) as orange crystals: mp 84.3–86.2° C. 1H NMR (acetone-d6/300 MHz) 9.96 (s, 1H), 8.06 (d, 1H, J=2 Hz), 8.02 (s, 1H), 7.99 (dd, 1H, J=8.5, 2.0 Hz), 7.24 (d, 1H, J=8.5 Hz), 5.99 (q, 1H, J=7.1 Hz), 4.43–4.25 (m, 2H), 1.34 (t, 3H, J=7.3 Hz). FABLRMS m/z 301 (M+H). EIHRMS m/z 300.0605 (M+, Calc'd 300.0609). Anal. Calc'd for C14H11F3O4: C, 56.01; H, 3.69. Found: C, 56.11; H, 3.73.

Workup

  1. temperaturethe reaction heated for 16 hours at 75° C
  2. temperatureAfter cooling to room temperature
  3. customthe reaction was partitioned between H2O and diethyl ether
  4. washThe organic phase was washed with saturated NaHCO3 solution, KHSO4 solution (0.25 M), brine
  5. additiontreated with decolorizing carbon (
  6. temperaturewarmed gently)
  7. dry with materialThe resulting black suspension was dried over MgSO4, vacuum
  8. filtrationfiltered through diatomaceous earth
  9. concentrationconcentrated in vacuo
  10. customyielding an orange crystalline mass
  11. customThis material was recrystallized from hot hexanes yielding the ester (1.51 g, 24%) as orange crystals

Sources & evidence

ORD record
ord-45524fabf623455e8f21f5978696aa42
Source dataset
uspto-grants-2006_09
Patent number
US07109211B2

Reaction notes

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