반응 #326271

ord-1ec872ec8fff4ae2b22a715216a91ce1

반응 조건

온도
91.5°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    세척washing solution (acetic acid solution)
  2. 2
    기타obtained from the Example 9
  3. 3
    온도The reaction solution was cooled to room temperature
  4. 4
    추출extracted
  5. 5
    세척The organic layer was washed with water
  6. 6
    건조a saturated aqueous solution of sodium hydrogen carbonate, and a saturated aqueous solution of sodium chloride in order, and dried over anhydrous magnesium sulfate
  7. 7
    기타The solvent was removed by distillation under reduced pressure
  8. 8
    기타to give a crude product, which
  9. 9
    기타The concentrated residues obtained
  10. 10
    기타were crystallized with chloroform-hexane

실험 절차

174.84 g [containing 0.351 g of (1R,2S,3R,5R,6R)-2-amino-2-cyano-3-[(3,4-dichloro benzyl)oxy]-6-fluoro bicyclo[3.1.0]hexane-6-carboxamide citrate (6b) and 3.853 g of (1R,2R,3R,5R,6R)-2-amino-2-cyano-3-[(3,4-dichloro benzyl)oxy]-6-fluorobicyclo[3.1.0]hexane-6-carboxamide citrate (8b)] of the 190.36 g of the filtrate and washing solution (acetic acid solution) obtained from the Example 9 was added with 174 mL of water and stirred for 4.5 hrs under heating at 90 to 93° C. The reaction solution was cooled to room temperature, added with ethyl acetate and water, and extracted. The organic layer was washed with water, a saturated aqueous solution of sodium hydrogen carbonate, and a saturated aqueous solution of sodium chloride in order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure to give a crude product, which was then subjected to silica gel column chromatography (eluent solution: chloroform:methanol=20:1). The concentrated residues obtained were crystallized with chloroform-hexane to obtain 2.07 g of (1R,3R,5R,6R)-3-[(3,4-dichloro benzyl)oxy]-6-fluoro-2-oxo bicyclo[3.1.0]hexane-6-carboxamide (5b) as a colorless solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08642777B2uspto-grants-2014_02