Reacción #61370

ord-aaef002ffb2a42bb8231e6616b3192f5

Disolventes

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    workup.STIRRINGit was stirred at the same temperature for additional 3 hours
  2. 2
    workup.WAITThe solution was left
  3. 3
    workup.STIRRINGstirring overnight
  4. 4
    TemperaturaWhile cooling on ice, to the reaction mixture
  5. 5
    workup.STIRRINGstirred at room temperature for additional 2 hours
  6. 6
    Extracciónwas extracted with ethyl acetate
  7. 7
    LavadoThe organic layer was washed sequentially with water and brine
  8. 8
    Secadodried over anhydrous magnesium sulfate
  9. 9
    Concentraciónconcentrated under reduced pressure
  10. 10
    LavadoThe concentrated residue was further washed with heptane

Procedimiento

7,8-difluoro-2-(4-propylcyclohexyl)chroman (3.82 g) obtained in Example 2 was dissolved in THF (38 mL). To the solution was added dropwise sec-BuLi (0.99 M solution, 15.5 mL) at −70 to −75° C. and stirred after the end of dropping at the same temperature for additional 1 hour. To the solution was added dropwise a THF solution (5 mL) of triisopropyl borate (2.15 g) at −70 to −75° C. After the end of dropping, it was stirred at the same temperature for additional 3 hours. Then temperature thereof was gradually raised to room temperature. The solution was left stirring overnight. While cooling on ice, to the reaction mixture was added 2 M hydrochloric acid and stirred at room temperature for additional 2 hours. The reaction mixture was poured to water, which was extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The concentrated residue was further washed with heptane to obtain crude 7,8-difluoro-6-dihydroxyboryl-2-(4-propylcyclohexyl)chroman. The product was used in a second step without purification.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US07429411B2uspto-grants-2008_09