Ammonium Chloride → 1,1-Dimethylethyl (2R,6S)-4-[(4-aminophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate

HRID 906366Notes

Reaction equation

HRID 906366 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][C@H:4]([CH3:18])[N:3]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[Cl-].[NH4+]>CO.O.[Fe]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:6]2[CH2:5][C@H:4]([CH3:18])[N:3]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[C@H:2]([CH3:1])[CH2:7]2)=[CH:10][CH:11]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 592622131,1-Dimethylethyl (2R,6S)-2,6-dimethyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate

Product 1

HCID 592622361,1-Dimethylethyl (2R,6S)-4-[(4-aminophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylateYield 70.4%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1,1-dimethylethyl (2R,6S)-2,6-dimethyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate (D27) (2.62 g, 7.53 mmol) in MeOH (25 ml) and water (25 ml) heated to 80° C. was added iron powder (1.26 g, 22.54 mmol) and ammonium chloride (2.01 g, 37.58 mmol). The reaction was stirred vigorously at 80° C. for 1.5 h and then the iron residues removed by filtration through Celite®. The filtrate was concentrated and the residue partitioned between DCM and water. The aqueous layer was further extracted with DCM (×2) and the combined organics were dried and concentrated to give the crude product as a yellow foam (2.01 g). Column chromatography eluting with 0-100% Et2O/petroleum ether gave the title compound (1.694 g). δH (CDCl3, 400 MHz) 7.12 (2H, d), 6.64 (2H, d), 4.05 (2H, m), 3.64 (2H, br. s), 3.36 (2H, s), 2.59 (2 h, d), 2.06 (2H, dd), 1.46 (9H, s), 1.27 (6H, d). MS (ES): MH+ 320.3, MNa+ 342.3.

Workup

  1. customthe iron residues removed by filtration through Celite®
  2. concentrationThe filtrate was concentrated
  3. customthe residue partitioned between DCM and water
  4. extractionThe aqueous layer was further extracted with DCM (×2)
  5. customthe combined organics were dried
  6. concentrationconcentrated
  7. customto give the crude product as a yellow foam (2.01 g)
  8. washColumn chromatography eluting with 0-100% Et2O/petroleum ether

Sources & evidence

ORD record
ord-f6454ea9da814aaf857b49528e3fa336
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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