반응 #42138

반응 방정식

4-(N-tert-butoxycarbonylaminomethyl)aniline

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

HATU

DIPEA

→

title intermediate

수율 94.0%

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

수율 94.0%

용매

TFA DCM

DMF

반응 조건

후처리

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

실험 절차

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).

출처