反応 #88931

ord-1100536bb7104000a14be99016408b0c

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度The mixture was cooled to 0° C.
  2. 2
    workup.STIRRINGstirred at RT for 1 h
  3. 3
    温度The mixture was cooled to 0° C.
  4. 4
    その他quenched by dropwise addition of water
  5. 5
    その他to give a gel that
  6. 6
    その他was partitioned between EtOAc/ether and brine/water/aqueous potassium sodium tartrate solution
  7. 7
    ろ過The insoluble salts were filtered off
  8. 8
    その他the phases separated
  9. 9
    抽出The aqueous phase was extracted with EtOAc (2×)
  10. 10
    洗浄the combined organic layers were washed with a 10% aqueous citric acid solution, saturated sodium bicarbonate solution and brine
  11. 11
    乾燥dried (Na2SO4)
  12. 12
    ろ過filtered
  13. 13
    その他evaporated in vacuo
  14. 14
    その他purified by FCC

実験手順

A solution of Intermediate 61a (2.88 g, 6.60 mmol) in DCM (50 mL) at 0° C. under N2 was treated dropwise with diisobutyl aluminium hydride (1.0M in THF, 16.6 mL, 16.6 mmol) and the mixture was stirred at RT overnight. The mixture was cooled to 0° C., then treated dropwise with another portion of diisobutyl aluminium hydride (1.0M in THF, 8.3 mL, 8.30 mmol) and stirred at RT for 1 h. The mixture was cooled to 0° C. and quenched by dropwise addition of water to give a gel that was partitioned between EtOAc/ether and brine/water/aqueous potassium sodium tartrate solution. The insoluble salts were filtered off and the phases separated. The aqueous phase was extracted with EtOAc (2×) and the combined organic layers were washed with a 10% aqueous citric acid solution, saturated sodium bicarbonate solution and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was pre-adsorbed onto diatomaceous earth and purified by FCC, using 0-15% EtOAc in cyclohexane, to give the title compound as a colorless oil (1.04 g, 39%). LCMS (Method 3): Rt 5.29 min, m/z 405 [MH+].

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09440974B2uspto-grants-2016_09