Reacción #942098

ord-3afe21b707e34efb8aecd4fbacd9c706

Disolventes

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    workup.ADDITIONTo a Parr bottle containing
  2. 2
    workup.STIRRINGAfter stirring for 2.5 days
  3. 3
    Temperaturathe mixture was cooled to −78° C.
  4. 4
    workup.STIRRINGAfter stirring at room temperature for 4 days
  5. 5
    workup.STIRRINGstirred at room temperature overnight
  6. 6
    Extracciónextracted with EtOAc (200 mL)
  7. 7
    SecadoThe extract was dried over MgSO4
  8. 8
    Filtraciónfiltered
  9. 9
    Concentraciónconcentrated in vacuo
  10. 10
    OtroPurification by silica chromatography (95:5 EtOAc:hexanes)

Procedimiento

To a Parr bottle containing a mixture of ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 21 a, Step 2 (1.00 g, 2.07 mmole), CuI (39 mg, 0.207 mmole), PdCl2(dppf)2.CH2Cl2 (167 mg, 0.0.207 mmole) and TEA (867 uL, 6.22 mmole) in anhydrous toluene (10 mL) was added at −78° C. 1-butyne (5 ml) and the bottle was sealed. After stirring for overnight at room temperature, additional CuI (390 mg, 2.07 mmole) and PdCl2(dppf)2.CH2Cl2 (1.67 g, 2.07 mmole) were added and the vessel was resealed. After stirring for 2.5 days, the mixture was cooled to −78° C. and additional CuI (200 mg, 1.05 mmole) and PdCI2(dppf)2.CH2Cl2 (0.500 g, 0.613 mmole), anhydrous toluene (10 mL) and 1-butyne (5 ml) were added and the vessel was resealed. After stirring at room temperature for 4 days, additional CuI (390 mg, 2.07 mmole) and PdCl2(dppf)2.CH2Cl2 (0.500 g, 0.613 mmole) were added and the vessel was resealed and stirred at room temperature overnight. The mixture was then poured into brine (100 mL) and extracted with EtOAc (200 mL). The extract was dried over MgSO4, filtered and concentrated in vacuo. Purification by silica chromatography (95:5 EtOAc:hexanes) gave the product as a crystalline solid: EIHRMS m/z 408.0773 (M+, C18H]4F6O4, Calc'd 408.0796).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US07259266B2uspto-grants-2007_08