反応 #332611

ord-b080f6c617d74125a6d08c595459593d

溶媒

反応条件

温度
0°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度then cooled again to −78° C
  2. 2
    その他at −78° C.
  3. 3
    その他at −78° C
  4. 4
    温度Allowed the solution to warm to −50° C.
  5. 5
    その他quenched with saturated ammonium chloride solution
  6. 6
    抽出Extracted mixture with ethyl acetate
  7. 7
    洗浄washed
  8. 8
    その他resulting organics with brine
  9. 9
    ろ過Dried organics over sodium sulfate, filtered
  10. 10
    その他evacuated filtrate under vacuum
  11. 11
    その他to give crude yellow oil
  12. 12
    その他The crude oil was purified on silica using 10-30% acetone in n-hexane as eluant

実験手順

Diisopropylamine (0.925 mL, 6.55 mmol) was added dropwise to a stirring solution of 2.5M n-butyllithium in hexane (2.495 mL, 6.24 mmol) in THF (10 mL) at −78° C. Allowed solution to warm to 0° C. for 10 minutes then cooled again to −78° C. Cannulated the prepared LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.6 g, 3.12 mmol) in THF (10 mL) at −78° C. Allowed the dark solution to stir for 20 minutes and then cannulated into a stirring solution of N-methoxy-N-methylpicolinamide (1.05 g, 6.24 mmol) in THF (10 mL) at −78° C. Allowed the solution to warm to −50° C. and then quenched with saturated ammonium chloride solution. Extracted mixture with ethyl acetate and washed resulting organics with brine. Dried organics over sodium sulfate, filtered, and evacuated filtrate under vacuum to give crude yellow oil. The crude oil was purified on silica using 10-30% acetone in n-hexane as eluant to give 1.3 g (67%) of the title compound as oil.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08658641B2uspto-grants-2014_02