Reaktion #42138

Reaktionsgleichung

4-(N-tert-butoxycarbonylaminomethyl)aniline

3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid

HATU

DIPEA

→

title intermediate

Ausbeute 94.0%

Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

Ausbeute 94.0%

Lösungsmittel

TFA DCM

DMF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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).

Quelle