Reaktion #157165

Reaktionsgleichung

DIPEA

4-chloro-3-nitropyridine

(3S,5R)-benzyl 3-(tert-butoxycarbonylamino)-5-fluoropiperidine-1-carboxylate

→

titled compound

Ausbeute 90.0%

tert-butyl (3S,5R)-5-fluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate

Ausbeute 90.0%

Lösungsmittel

methanol

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 33 mL of isopropanol
5. 5
   workup.STIRRINGThe reaction mixture was stirred at 80° 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 (5% methanol in EtOAc:hexanes=1:1)

Vorschrift

To a solution of (3S,5R)-benzyl 3-(tert-butoxycarbonylamino)-5-fluoropiperidine-1-carboxylate (1 eq) in 28 methanol was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere for 1 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 33 mL of isopropanol and DIPEA (2.5 eq) and 4-chloro-3-nitropyridine (1.5 eq) were added. The reaction mixture was stirred at 80° 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 (5% methanol in EtOAc:hexanes=1:1) to give the titled compound (90%). LC/MS (m/z): 341.1 (MH+). HPLC: Rt: 2.115 min.

Quelle