Réaction #157782

ord-b5a5e36482fd46f1911660719c397f3b

Conditions de réaction

Température
-78°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

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

Mode opératoire

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%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US08822503B2uspto-grants-2014_09