1,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate → (R)-tert-Butyl(1-(3-amino-4-(methylamino)benzoyl)piperidin-3-yl)carbamate

HRID 2275006Notes

Reaction equation

HRID 2275006 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:26])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][CH3:22])=[C:17]([N+:23]([O-])=O)[CH:16]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:26])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][CH3:22])=[C:17]([NH2:23])[CH:16]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 863401791,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate

Product 1

HCID 118178597(R)-tert-Butyl(1-(3-amino-4-(methylamino)benzoyl)piperidin-3-yl)carbamateYield 36.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

(R)-tert-Butyl(1-(4-(methylamino)-3-nitrobenzoyl)piperidin-3-yl)carbamate (3.79 g, 10.02 mmol) was dissolved in ethanol (75 mL) and added to a flushed hydrogenation flask containing Pd/C (380 mg, 0.411 mmol). The resultant mixture was flushed with nitrogen/vacuum 3 times, then stirred under an atmosphere of hydrogen at room temperature for 24 hours. The reaction mixture was flushed from hydrogen atmosphere with nitrogen/vacuum three times. To this solution Celite (33 g) was added and stirred for 2 min. then filtered under vacuum. The solution was concentrated under vacuum to give a crude product that was purified on a 100 g SNAP cartridge using SP4 column chromotography. The column was eluted with 0-6% 2M NH3 in MeOH in DCM over 25CV. The appropriate fractions were combined and concentrated in vacuo to give a product that was further purified using SP4 column chromotography on a 100 g SNAP cartridge. The column was eluted with 0-100% EtOAc in cyclohexane over 15CV followed by 100% EtOAc 5CV followed by 0-6% 2M NH3 in MeOH in DCM over 15CV. The appropriate fractions were combined and concentrated in vacuo to give the title compound as a pink solid (1.26 g).

Workup

  1. additionadded to a flushed hydrogenation flask
  2. customThe resultant mixture was flushed with nitrogen/vacuum 3 times
  3. customThe reaction mixture was flushed from hydrogen atmosphere with nitrogen/vacuum three times
  4. additionTo this solution Celite (33 g) was added
  5. stirringstirred for 2 min.
  6. filtrationthen filtered under vacuum
  7. concentrationThe solution was concentrated under vacuum
  8. customto give a crude product that
  9. customwas purified on a 100 g SNAP cartridge
  10. washThe column was eluted with 0-6% 2M NH3 in MeOH in DCM over 25CV
  11. concentrationconcentrated in vacuo
  12. customto give a product that
  13. customwas further purified
  14. washThe column was eluted with 0-100% EtOAc in cyclohexane over
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-33ea158efd08424683c50ed18b7d2424
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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