반응 #836866

ord-92a6a8a20ca448c4bb5cffe7108e740c

반응 조건

온도
-78°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

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

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07402698B2uspto-grants-2008_07