Reaktion #2007347

Reaktionsgleichung

(3S,5S)-benzyl 3-(benzoyloxy)-5-(tert-butoxycarbonylamino)-piperidine-1-carboxylate

methanol

DIPEA

4-chloro-3-nitropyridine

→

(3S,5S)-5-(tert-butoxycarbonylamino)-1-(3-nitropyridin-4-yl)-piperidin-3-yl benzoate

Ausbeute 90.0%

Lösungsmittel

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe crude solids were filtered through a pad of Celite on a paper
2. 2
   Waschenwashed with MeOH
3. 3
   Einengenconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in 20 mL of isopropanol
5. 5
   workup.STIRRINGThe reaction mixture was stirred at 75° C. for 2 hours, at which
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   workup.ADDITIONThe residue was diluted with 150 mL of EtOAc
8. 8
   Waschenwashed with brine
9. 9
   Trocknendried over anhydrous MgSO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo
12. 12
    SonstigeThe crude residue was purified by flash chromatography (EtOAc:hexanes=1:1)

Vorschrift

To a solution of (3S,5S)-benzyl 3-(benzoyloxy)-5-(tert-butoxycarbonylamino)-piperidine-1-carboxylate (1 eq) in 15 methanol and 15 mL of EtOAc was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere for 4 hours. The crude solids were filtered through a pad of Celite on a paper lined Buchner funnel, washed with MeOH, then concentrated in vacuo. The residue was dissolved in 20 mL of isopropanol and DIPEA (1.8 eq) and 4-chloro-3-nitropyridine (1.2 eq) were added. The reaction mixture was stirred at 75° C. for 2 hours, at which point the reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was diluted with 150 mL of EtOAc, washed with brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=1:1) to yield (3S,5S)-5-(tert-butoxycarbonylamino)-1-(3-nitropyridin-4-yl)-piperidin-3-yl benzoate (90%). LC/MS (m/z): 443.2 (MH+). HPLC: Rt: 2.89 min.

Quelle