반응 #68019

ord-9af1d405f51242f9898f02c277824429

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.ADDITIONwere added
  2. 2
    온도with reflux
  3. 3
    온도by heating under a nitrogen atmosphere
  4. 4
    workup.STIRRINGthe mixture was stirred at 90 to 100° C. for 1 hour
  5. 5
    workup.STIRRINGthe mixture was stirred at 90 to 100° C. for 1 hour
  6. 6
    기타the organic layer was separated
  7. 7
    추출the aqueous layer was extracted with ethyl acetate
  8. 8
    세척the resultant solution was washed sequentially with water
  9. 9
    건조an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate
  10. 10
    기타the solvent was removed under reduced pressure
  11. 11
    기타The residue thus obtained
  12. 12
    기타was purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20]

실험 절차

To 30 mL of a 1,4-dioxane solution containing 2.4 g of 2-chloro-5-fluoro-3-((methoxymethoxy)methyl)-6-methylpyridine, 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was stirred for 2 hours with reflux by heating under a nitrogen atmosphere. Thereto was added 30 mL of N,N-dimethylformamide, and the mixture was stirred at 90 to 100° C. for 1 hour. Thereto were added 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0), and the mixture was stirred at 90 to 100° C. for 1 hour. Water and ethyl acetate were added thereto, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed sequentially with water and an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20] to obtain 1.8 g of a yellow oily substance, 3-fluoro-5-((methoxymethoxy)methyl)-2-methylpyridine.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08524738B2uspto-grants-2013_09