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

HRID 1920179Notes

Reaction equation

HRID 1920179 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C@@H:13]([F:15])[CH2:12][N:11]([C:16](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:41]=[CH:40][N:39]=[CH:38][C:37]=1[N+:42]([O-:44])=[O:43]>[Pd].CO>[F:15][C@H:13]1[CH2:12][N:11]([C:16]2[CH:41]=[CH:40][N:39]=[CH:38][C:37]=2[N+:42]([O-:44])=[O:43])[CH2:10][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:14]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 68919599HCID 68919599, compound

Product 1

HCID 68920425tert-butyl (3S,5R)-5-fluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamateYield 90%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

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 yield tert-butyl(3S,5R)-5-fluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate (90%). LC/MS (m/z): 341.1 (MH+). HPLC: Rt: 2.12 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 33 mL of isopropanol
  5. stirringThe reaction mixture was stirred at 80° C. for 2 hours, at which
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with 150 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)

Sources & evidence

ORD record
ord-417c9b34b2ab42d2ba9b1e408f2bbf5c
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

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