Реакция #42138

ord-6f6c62e594e144db91daf6c248e0d417

Растворители

Условия реакции

Температура
50°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    Другоеthe solvent was removed under reduced pressure
  2. 2
    workup.DISSOLUTIONThe resulting residue was dissolved in DCM (20 mL)
  3. 3
    Промывкаwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  4. 4
    СушкаThe organic phase was then dried over MgSO4
  5. 5
    Другоеthe solvent was removed under reduced pressure
  6. 6
    ДругоеThe crude product was purified by flash chromatography (5-10% MeOH/DCM)
  7. 7
    Другоеto give a solid, which
  8. 8
    workup.STIRRINGstirred at room temperature for 2 hours
  9. 9
    ДругоеThe solvent was then removed under reduced pressure
  10. 10
    workup.DISSOLUTIONthe crude residue was dissolved in DCM (30 mL)
  11. 11
    Промывкаwashed with 1N NaOH (15 mL)
  12. 12
    ДругоеThe organic phase was separated
  13. 13
    Сушкаdried over MgSO4
  14. 14
    Фильтрацияfiltered
  15. 15
    Другоеthe solvent was removed under reduced pressure

Методика

To a stirred solution of 4-(N-tert-butoxycarbonylaminomethyl)aniline (756 mg, 3.4 mmol), 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (1.5 g, 4.08 mmol; prepared as described in Preparation 11) and HATU (1.55 g, 4.08 mmol) in DMF (6.8 mL), was added DIPEA (770 mL, 4.42 mmol). The reaction mixture was stirred at 50° C. overnight, and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic phase was then dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (5-10% MeOH/DCM) to give a solid, which was dissolved in TFA/DCM (25%, 30 mL) and stirred at room temperature for 2 hours. The solvent was then removed under reduced pressure and the crude residue was dissolved in DCM (30 mL) and washed with 1N NaOH (15 mL). The organic phase was separated, dried over MgSO4, filtered and the solvent was removed under reduced pressure to give 1.5 g of the title intermediate (94% yield over 2 steps).

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US07728144B2uspto-grants-2010_06