反応 #57117

ord-6946c7709a474ac0942045de99ad099d

反応条件

温度
-78°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.STIRRINGThe reaction was stirred at −78° C. for 45 min
  2. 2
    その他after which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate
  3. 3
    その他the tetrahydrofuran was removed in vacuo
  4. 4
    その他The resulting residue was partitioned between water and ethyl acetate
  5. 5
    その他the layers were separated
  6. 6
    抽出The aqueous layer was extracted with ethyl acetate (3×30 mL)
  7. 7
    乾燥the combined organic extracts were dried over magnesium sulfate
  8. 8
    濃縮concentrated in vacuo
  9. 9
    その他the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc)

実験手順

A solution of tert-butyl 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylate (466 mg, 1.60 mmol) in dry tetrahydrofuran (6 mL) under nitrogen was cooled to −78° C. and treated dropwise with a solution of n-butyllithium (2.5 M in hexanes, 0.70 mL, 1.75 mmol). The resulting solution was stirred at −78° C. for 1 h. The reaction was then treated with a solution of cyclohexanone (174 mg, 1.77 mmol) in dry tetrahydrofuran (0.8 mL). The reaction was stirred at −78° C. for 45 min, after which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate, and the tetrahydrofuran was removed in vacuo. The resulting residue was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×30 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc) to yield 484 mg (78%) tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-pyridin-2-yl-ethyl]-piperazine-1-carboxylate as a colorless oil.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07419980B2uspto-grants-2008_09