Reacción #42138

Ecuación de reacción

4-(N-tert-butoxycarbonylaminomethyl)aniline

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

HATU

DIPEA

→

title intermediate

Rendimiento 94.0%

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

Rendimiento 94.0%

Disolventes

TFA DCM

DMF

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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).

Fuente