ethyl 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylate → ethyl 6-(pentafluoroethyl)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate

HRID 722312Notes

Reaction equation

HRID 722312 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]([F:8])([F:7])[C:4]([O-])=O.[K+].IC1[CH:14]=[CH:15][C:16]2[O:21][CH:20]([C:22]([F:25])([F:24])[F:23])[C:19]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:18][C:17]=2[CH:31]=1>C1(C)C=CC=CC=1.CN(C=O)C.[Cu]I>[F:7][C:3]([F:8])([C:4]1[CH:14]=[CH:15][C:16]2[O:21][CH:20]([C:22]([F:25])([F:23])[F:24])[C:19]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:18][C:17]=2[CH:31]=1)[C:2]([F:10])([F:9])[F:1]

Participants

6

Reactant 2

HCID 21883584ethyl 6-iodo-2-trifluoromethyl-2H-1-benzopyran-3-carboxylateHCID 23667659Propanoic acid, 2,2,3,3,3-pentafluoro-, potassium salt (1:1)

Product 1

HCID 21883728ethyl 6-(pentafluoroethyl)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Potassium pentafluoropropionate (0.476 g, 2.35 mmol) was dissolved in toluene (6 mL) and DMF (6 mL). The vessel was fitted with a distilling head, and CuI (0.471 g, 2.474 mmol) was added with stirring. The reaction was heated to 120° C., removing the toluene by distillation. Ethyl 6-iodo-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate (Example 72, Step 3) (0.469 g, 1.178 mmol) was added and the reaction was heated to 150° C. for 2 hours. The reaction was allowed to cool to room temperature and was partitioned between diethyl ether and H2O. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica gel 60, eluant: hexanes-ethyl acetate, 8:1) yielding, upon concentration of the solution, the desired ester (0.096 g, 21%) as a tan solid mass of suitable purity to use without further purification: 1H NMR (acetone-d6/300 MHz) 8.04 (s, 1H), 7.91 (d, 1H, J=2.2 Hz), 7.74 (dd, 1H, J=8.7, 2.2 Hz), 6.00 (q, 1H, J=7.1 Hz), 4.42−4.24 (m, 2H), 1.34 (t, 3H, J=7.3 Hz).

Workup

  1. additionwas added
  2. customremoving the toluene
  3. distillationby distillation
  4. temperaturethe reaction was heated to 150° C. for 2 hours
  5. temperatureto cool to room temperature
  6. customwas partitioned between diethyl ether and H2O
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by flash chromatography (silica gel 60, eluant: hexanes-ethyl acetate, 8:1)
  11. customyielding, upon concentration of the solution
  12. customthe desired ester (0.096 g, 21%) as a tan solid mass of suitable purity to use without further purification

Sources & evidence

ORD record
ord-ad059958e1944fceb813b65fe8d0d05b
Source dataset
uspto-grants-2006_11
Patent number
US07138411B2

Reaction notes

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