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

HRID 2424624Notes

Reaction equation

HRID 2424624 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 a solution of D1 (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 (4 g) catalyst 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 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, m), 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. extractionfurther extracted with DCM (×2)
  6. washThe combined organics were washed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-98f544bc9e6645268ecc5669f3698580
Source dataset
uspto-grants-2011_06
Patent number
US07964597B2

Reaction notes

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