Ethyl Acetate → Tert-butyl 4-(4-(3-hydroxypropyl)phenyl)piperazine-1-carboxylate

HRID 452304Notes

Reaction equation

HRID 452304 reaction equation
[OH:1][CH2:2][C:3]#[C:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:7][CH:6]=1.CCOC(C)=O>CCO.[Pd]>[OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]2)=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 15851174Tert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylate

Product 1

HCID 59470519Tert-butyl 4-(4-(3-hydroxypropyl)phenyl)piperazine-1-carboxylateYield 71%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of tert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylate (3.2 g, 10.11 mmol) in EtOH (253 mL) was added EtOAc (200) and Pd/C (10% mol on carbon, 3.2 g). The reaction mixture was shaken at 50 psi of H2 atm. overnight. The next day, the catalyst was removed from the reaction mixture via a filtration over a pad of celite and the filtrate was concentrated to yield a crude oil. Purification of the crude material using silica gel chromatography (gradient method of 0%-100% EtOAc in hexanes) yielded tert-butyl 4-(4-(3-hydroxypropyl)phenyl)piperazine-1-carboxylate as an off-white solid (2.3 g, 71% yield). 1H NMR (300 MHz, CDCl3): δ 7.11 (d, 2H, J=8.7 Hz), 6.89 (d, 2H, J=8.7 Hz), 3.67 (br t, 2H, J=6.4 Hz), 3.58 (dd, 4H, J=5.2, 5.1 Hz), 3.09 (dd, 4H, J=5.2, 5.0 Hz), 2.65 (dd, 2H, J=8.0, 7.4 Hz), 1.87 (m, 2H), 1.49 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 154.9, 149.7, 133.9, 129.3, 117.1, 80.1, 62.4, 49.9, 44.1, 34.5, 31.3, 28.6; HRMS calcd for C18H28N2O3: 321.21727 found 321.2174.

Workup

  1. customovernight
  2. customThe next day, the catalyst was removed from the reaction mixture via a filtration over a pad of celite
  3. concentrationthe filtrate was concentrated
  4. customto yield a crude oil
  5. customPurification of the crude material

Sources & evidence

ORD record
ord-366e6c7904814090ae535243a5d9dda7
Source dataset
uspto-grants-2013_07
Patent number
US08491868B2

Reaction notes

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