Diisopropylethylamine → (S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate

HRID 73533Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73533
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][N:13]([C:15]([O-])=O)[CH2:12][C:11]([F:19])([F:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.ClC1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37]>CO.CCOC(C)=O.[Pd]>[F:18][C:11]1([F:19])[CH2:12][N:13]([C:15]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[N+:36]([O-:38])=[O:37])[CH2:14][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 866447355-(Tert-butoxycarbonylamino)-3,3-difluoropiperidine-1-carboxylate

Produkt 1

HCID 67501048(S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamateAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 5-(tert-butoxycarbonylamino)-3,3-difluoropiperidine-1-carboxylate (1 eq) in 5 mL of methanol and 5 mL of EtOAc was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere overnight. 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 5 mL of isopropanol and DIPEA (2.0 eq) and 4-chloro-3-nitropyridine (1.5 eq) were added. The reaction mixture was stirred at 70° C. for 3 hours, at which point the reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was diluted with 120 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 yield (S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate (19%). LC/MS (m/z): 359.0 (MH+), Rt:0.65 min.

Aufarbeitung

  1. filtrationThe crude solids were filtered through a pad of Celite on a paper
  2. washwashed with MeOH
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 5 mL of isopropanol
  5. stirringThe reaction mixture was stirred at 70° C. for 3 hours, at which
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with 120 mL of EtOAc
  8. washwashed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was purified by flash chromatography (5% methanol in EtOAc:hexanes=1:1)

Quellen und Nachweise

ORD-Eintrag
ord-46b7282d3bc348dda02f9c6c398d01ff
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829193B2

Notizen zur Reaktion

Wird geladen…