반응 #155592

ord-c3b719c3ed9c4ec89331bebedfe9b317

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타partitioned between ethyl acetate (25 mL)
  2. 2
    기타The layers were separated
  3. 3
    추출the aqueous layer was extracted further with ethyl acetate (3×25 mL)
  4. 4
    세척The combined organics were then washed sequentially with water (100 mL) and with brine (100 mL)
  5. 5
    건조dried over sodium sulfate
  6. 6
    여과filtered
  7. 7
    농축The filtrate was concentrated under reduced pressure
  8. 8
    기타to yield a white solid
  9. 9
    세척the resulting solution was washed with 1 N sodium hydroxide (3×25 mL), water (100 mL), and brine (100 mL)
  10. 10
    건조The organic layer was dried over sodium sulfate
  11. 11
    여과filtered
  12. 12
    농축concentrated under reduced pressure

실험 절차

Lithium triethylborohydride (1.13 mL, 1.13 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C27) (60 mg, 0.11 mmol) in tetrahydrofuran (4 mL). The reaction mixture was allowed to stir at room temperature for 16 hours and then partitioned between ethyl acetate (25 mL) and a saturated aqueous solution of sodium bicarbonate (50 mL). The layers were separated and the aqueous layer was extracted further with ethyl acetate (3×25 mL). The combined organics were then washed sequentially with water (100 mL) and with brine (100 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield a white solid. The organic crude was re-dissolved in dichloromethane (20 mL) and the resulting solution was washed with 1 N sodium hydroxide (3×25 mL), water (100 mL), and brine (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the product as an orange solid (60 mg), which was taken directly to the following step. LCMS m/z 514 [M+H+].

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08822456B2uspto-grants-2014_09