Potassium Hydroxide → tert-Butyl 4-(3-amino-4-(aminomethyl)phenyl)piperazine-1-carboxylate

HRID 1406618Notes

Reaction equation

HRID 1406618 reaction equation
C([NH:4][C:5]1[CH:6]=[C:7]([N:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:8]=[CH:9][C:10]=1[CH2:11][NH:12]C(=O)C)(=O)C.[OH-].[K+]>C(O)C>[NH2:4][C:5]1[CH:6]=[C:7]([N:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]2)[CH:8]=[CH:9][C:10]=1[CH2:11][NH2:12]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 131732195tert-Butyl 4-(3-acetamido-4-(acetamidomethyl)phenyl)piperazine-1-carboxylate

Product 1

HCID 131732196tert-Butyl 4-(3-amino-4-(aminomethyl)phenyl)piperazine-1-carboxylateYield 83.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of compound 19 (1.5 g, 3.85 mmol) in ethanol (20 mL) at room temperature was added a solution of KOH (3M, 25 mL), and the reaction was refluxed for 12 h. The reaction was cooled to room temperature, ice cold water was added, and the solution was extracted with ethyl acetate (30 mL×2). The organic layer was washed with brine (15 mL), dried over Na2SO4 and evaporated to get a brown oil material, which was resolved over silica column, eluting with ethyl acetate:hexanes (8:2), and then changing to ethyl acetate (100%) to obtain 0.98 g (83%) of 20 as a dark brown gum. IR (KBr) νmax. cm−1: 3060 (Ar-H), 1690 (C═O), 1616, 1514, 1417 (C═C). 1H NMR (500 MHz, CDCl3) δ=1.46 (s, 9H, (CH3)3C); 2.90 (m, 4H, 2CH2); 3.49 (m, 4H, 2CH2), 3.90 (s, 2H, CH2); 5.30 (br. s, 4H, 2NH2); 6.59 (d, 1H, J=8.2 Hz, H-5); 6.68 (dd, 1H, J=2.6, 8.2 Hz, H-6); 6.80 (d, 1H, J=2.6, H-2); 13C NMR (125.7 MHz, CDCl3) δ=28.37 (CH3)3C), 42.10 (CH2), 44.01 (CH2), 50.87 (CH2), 79.64 (CH3)3C), 117.29 (C-2), 117.79 (C-6), 119.88 (C-4), 120.36 (C-5), 139.80 (C-3), 144.15 (C-1), 154.67 (C═O). Calculated (%) for C16H26N4O2(306.21); C, 62.72; H, 8.55; N, 18.29. found (%) C, 62.63; H, 8.63; N, 18.20.

Workup

  1. temperaturethe reaction was refluxed for 12 h
  2. additionice cold water was added
  3. extractionthe solution was extracted with ethyl acetate (30 mL×2)
  4. washThe organic layer was washed with brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto get a brown oil material, which
  8. washeluting with ethyl acetate:hexanes (8:2)

Sources & evidence

ORD record
ord-02e5ef39b64c4e11a91d7b9282cf0630
Source dataset
uspto-grants-2014_12
Patent number
US08916704B1

Reaction notes

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