Reaktion #157782

ord-b5a5e36482fd46f1911660719c397f3b

Reaktionsbedingungen

Temperatur
-78°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.ADDITIONwas added
  2. 2
    workup.STIRRINGthe mixture was stirred at −78° C. to 0° C. for one hour
  3. 3
    Extraktionfollowed by extraction with ethyl acetate
  4. 4
    WaschenThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  5. 5
    Trocknendried over anhydrous magnesium sulfate
  6. 6
    Filtrationfiltered
  7. 7
    SonstigeThe solvent was then evaporated under reduced pressure
  8. 8
    SonstigeThe residue was purified by silica gel column chromatography (hexane:chloroform=1:1)

Vorschrift

A 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (4.0 mL) was added to a solution of 5-({[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]methyl}sulfonyl)-1-phenyl-1H-tetrazole obtained in Reference Example 3-1 (2.01 g) in tetrahydrofuran (20 mL) in a nitrogen gas stream at −78° C., and the mixture was stirred at −78° C. for one hour. A solution of (5-cyclopropyl-6-methoxypyridin-2-yl)(4-ethylphenyl)methanone obtained in Reference Example 1-53 (700 mg) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at −78° C. to 0° C. for one hour. The reaction solution was poured into a saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:chloroform=1:1) to give 3-cyclopropyl-6-[(E)-2-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]-1-(4-ethylphenyl)ethenyl]-2-methoxypyridine as a colorless amorphous (270 mg, 24%).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08822503B2uspto-grants-2014_09