Diethyl Ether → HCID 21883586, compound

HRID 2214880Notes

Reaction equation

HRID 2214880 reaction equation
Br[C:2]1[C:11]2[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7][C:6]=2[CH:5]=[C:4]([Cl:21])[CH:3]=1.[F-].[NH4+].[CH2:24](OCC)[CH3:25]>C1(C)C=CC=CC=1>[CH:19]([O:18][C:16]([C:8]1[CH:9]([C:12]([F:15])([F:14])[F:13])[O:10][C:11]2[C:2]([CH:24]=[CH2:25])=[CH:3][C:4]([Cl:21])=[CH:5][C:6]=2[CH:7]=1)=[O:17])=[CH2:20]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 25516Ammonium fluorideHCID 21883624HCID 21883624, compound

Product 1

HCID 21883586HCID 21883586, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a 100 mL round bottomed flask under N2, ethyl 8-bromo-6-chloro-2-trifluoromethyl-2H-benzopyran-3-carboxylate (Example 74, Step 1)(2.21 g, 5.73 mmol) was dissolved in toluene (30 mL of anhydrous reagent). Tetrakis (triphenylphosphine)palladium(0) (0.132 g, 0.115 mmol) was added, followed by tributylethyenylstannane (2.0 g, 6.31 mmol). The resulting solution was heated to reflux for 5 hours. The reaction mixture was allowed to cool to room temperature, was poured into 50 mL of 20% ammonium fluoride solution and stirred for one hour. Diethyl ether (100 mL) was added and the mixture was washed with water (2×50 mL). The organic phase was dried over MgSO4, filtered, and evaporated to yield a yellow oil. The crude material was purified by flash chromatography (0.5% ethyl acetate in hexanes) to afford the ester as a yellow solid (0.86 g, 45%): mp 75.9–77.2° C. 1H NMR (CDCl3/300 MHz) 7.64 (s, 1H), 7.45 (d, 1H, J=2.5 Hz), 7.12 (d, 1H, J=2.6 Hz), 6.92 (dd, 1H, J=17.7 Hz, 11.3 Hz), 5.81 (d, 1H, J=17.7 Hz), 5.76 (q, 1H, J=6.8 Hz), 5.41 (d, 2H, J=11.1 Hz), 4.36–4.29 (m, 2H), 1.36 (t, 3H, J=7.3 Hz). FABLRMS m/z 350.1 (M+NH4+). ESHRMS m/z 350.0796 (M+NH4+, Calc'd. 350.0771). Anal. Calc'd. for C15H12ClF3O3+4.07% H2O: C, 51.95; H, 3.94. Found: C, 51.67; H, 3.69.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 5 hours
  3. washthe mixture was washed with water (2×50 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a yellow oil
  8. customThe crude material was purified by flash chromatography (0.5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-308286158ad04266972ad5b80dd9b663
Source dataset
uspto-grants-2006_09
Patent number
US07109211B2

Reaction notes

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