Methanol → HCID 67501615, compound

HRID 73528Notes

Reaction equation

HRID 73528 reaction equation
[C:1]([O:9][C@H:10]1[CH2:15][C@H:14]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][N:12](C(OCC2C=CC=CC=2)=O)[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.CCN(C(C)C)C(C)C.Cl[C:46]1[CH:51]=[CH:50][N:49]=[CH:48][C:47]=1[N+:52]([O-:54])=[O:53]>[Pd].CCOC(C)=O>[C:1]([O:9][C@H:10]1[CH2:15][C@H:14]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][N:12]([C:46]2[CH:51]=[CH:50][N:49]=[CH:48][C:47]=2[N+:52]([O-:54])=[O:53])[CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 68920219(3S,5S)-benzyl 3-(benzoyloxy)-5-(tert-butoxycarbonylamino)-piperidine-1-carboxylate

Product 1

HCID 67501615HCID 67501615, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

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.

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 20 mL of isopropanol
  5. stirringThe reaction mixture was stirred at 75° 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 (EtOAc:hexanes=1:1)

Sources & evidence

ORD record
ord-0c9e0a4c9b6c4e2ca3c925b5a6eb54c9
Source dataset
uspto-grants-2014_09
Patent number
US08829193B2

Reaction notes

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