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

HRID 1920172Notes

Reaction equation

HRID 1920172 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C:13](=[CH:15][CH3:16])[CH2:12][N:11]([C:17](OCC2C=CC=CC=2)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.ClC1[CH:42]=[CH:41][N:40]=[CH:39][C:38]=1[N+:43]([O-:45])=[O:44]>C(O)C.CCOC(C)=O.[Pd]>[CH2:15]([C@H:13]1[CH2:12][N:11]([C:17]2[CH:42]=[CH:41][N:40]=[CH:39][C:38]=2[N+:43]([O-:45])=[O:44])[CH2:10][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:14]1)[CH3:16]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 68922866(S)-benzyl 3-(tert-butoxycarbonylamino)-5-ethylidenepiperidine-1-carboxylate

Product 1

HCID 68925412tert-butyl (3S,5R)-5-ethyl-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamateYield 91%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-benzyl 3-(tert-butoxycarbonylamino)-5-ethylidenepiperidine-1-carboxylate (1 eq) in 5.5 mL of ethanol and 5.5 mL of EtOAc was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere for 45 minutes. 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 1.4 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. overnight, 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 (EtOAc:hexanes=1:1) to yield tert-butyl(3S,5R)-5-ethyl-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate (91%). LC/MS (m/z): 351.2 (MH+), Rt: 0.75 min.

Workup

  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 1.4 mL of isopropanol
  5. stirringThe reaction mixture was stirred at 80° C. overnight, 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 (EtOAc:hexanes=1:1)

Sources & evidence

ORD record
ord-5e548e5592694325844a827f36433813
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

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