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

HRID 906358Notes

Reaction equation

HRID 906358 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][N:3]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[OH-].[K+]>CO.[Pd]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:6]2[CH2:5][CH2:4][N:3]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:2]([CH3:1])[CH2:7]2)=[CH:10][CH:11]=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 98.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To 1,1-dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate (D21) (4.62 g, 13.78 mmol) and KOH (7.79 g, 138.8 mmol) in MeOH (100 mL) was added wet (50% w/w water) 10% Pd/C catalyst (4 g) and the mixture was hydrogenated at room temperature and atmospheric pressure for 40 minutes. The catalyst was removed by filtration and the filtrate concentrated in vacuo. The residue was partitioned between DCM and water and aqueous layer was further extracted with DCM (×2). The combined organics were washed with brine, dried and concentrated to give the title compound as a colourless gum (4.14 g) which was used in the next step without further purification. δH (CDCl3, 400 MHz) 7.10 (2H, d), 6.64 (2H, d), 4.16 (1H, br.s), 3.78 (1H, d), 3.62 (2H, s), 3.42 (1H, d), 3.28 (1H, d), 3.08 (1H, td), 2.74 (1H, m), 2.58 (1H, m), 2.06 (1H, dd), 1.95 (1H, m), 1.46 (9H, s), 1.21 (3H, d).

Workup

  1. customwas hydrogenated at room temperature
  2. customThe catalyst was removed by filtration
  3. concentrationthe filtrate concentrated in vacuo
  4. customThe residue was partitioned between DCM and water and aqueous layer
  5. extractionwas further extracted with DCM (×2)
  6. washThe combined organics were washed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1948d8ff58e0403fb62d7aee82629009
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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