Potassium Hydroxide → 1,1-Dimethylethyl (2S)-4-[(4-aminophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 906359Notes

Reaction equation

HRID 906359 reaction equation
[OH-].[K+].[CH3:3][C@H:4]1[CH2:9][N:8]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=2)[CH2:7][CH2:6][N:5]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>O.CO>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:8]2[CH2:7][CH2:6][N:5]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@@H:4]([CH3:3])[CH2:9]2)=[CH:12][CH:13]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 592622041,1-Dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate

Product 1

HCID 592622171,1-Dimethylethyl (2S)-4-[(4-aminophenyl)methyl]-2-methyl-1-piperazinecarboxylateYield 93.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of potassium hydroxide (16.5 g, 0.29 mol) in water (35 mL) was added dry 10% Pd/C catalyst (10 g). MeOH (150 mL) was added and the mixture was hydrogenated at room temperature and atmospheric pressure for 15-20 minutes. 1,1-Dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate (D21) (10 g, 29.8 mmol) in MeOH (165 mL) was added and the reaction was hydrogenated for a total of 5 hrs. The catalyst was removed by filtration, washed with MeOH and water, and the filtrate/washings were concentrated in vacuo. The residue was partitioned between DCM and water and aqueous layer was further extracted with DCM. The combined organics were washed with brine, dried and concentrated to give the title compound as a colourless gum (8.49 g) which was used in the next step without further purification.

Workup

  1. dry with materialdry 10% Pd/C catalyst (10 g)
  2. additionMeOH (150 mL) was added
  3. customwas hydrogenated at room temperature
  4. customwas hydrogenated for a total of 5 hrs
  5. customThe catalyst was removed by filtration
  6. washwashed with MeOH and water
  7. concentrationthe filtrate/washings were concentrated in vacuo
  8. customThe residue was partitioned between DCM and water and aqueous layer
  9. extractionwas further extracted with DCM
  10. washThe combined organics were washed with brine
  11. customdried
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-83723bdd0b5b4570bf773c3ab89240e6
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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