Dimethylformamide → Tert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylate

HRID 452303Notes

Reaction equation

HRID 452303 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:21]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:26]=CC=C[CH:22]=1.CN(C=[O:44])C>[Pd](Cl)Cl.[Cu](I)I>[OH:44][CH2:22][C:21]#[C:26][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 2795511Tert-butyl 4-(4-iodophenyl)piperazine-1-carboxylate

Product 1

HCID 15851174Tert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylateYield 75%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 83717Copper iodideCatalyst

Procedure

To a slurry of tert-butyl 4-(4-iodophenyl)piperazine-1-carboxylate (200 mg, 0.515 mmol), triphenylphosphine (1.4 mg, 0.005 mmol), and palladium chloride (0.5 mg, 0.003 mmol) in DEA (2 mL) was added DMF (400 μL) and copper iodide (1 mg, 0.005 mmol). The reaction mixture stirred at room temperature for 24 h. The next day, the reaction mixture was concentrated and purified using silica gel chromatography (gradient method 0%-100% EtOAc in hexanes) to afford tert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylate as a yellow solid (92 mg, 75% yield based on recovered starting material). 1H NMR (300 MHz, CDCl3): δ 7.34 (d, 2H, J=8.8 Hz), 6.82 (d, 2H, J=8.9 Hz), 4.48 (d, 2H, J=5.6 Hz), 3.57 (dd, 4H, J=5.5., 4.9 Hz), 3.18 (dd, 4H, J=5.4, 5.0 Hz), 1.87 (t, 1H, J=5.7 Hz), 1.49 (s, 9H); 13C NMR (75 MHz, CDCl3): δ 154.7, 150.9, 132.8, 115.5, 113.1, 85.9, 80.0, 51.7, 48.4, 44.8, 28.4; FIRMS calcd for C18H24N2O3: 317.18597 found 317.1861.

Workup

  1. concentrationThe next day, the reaction mixture was concentrated
  2. custompurified
  3. customto afford
  4. customtert-butyl 4-(4-(3-hydroxyprop-1-ynyl)phenyl)piperazine-1-carboxylate as a yellow solid (92 mg, 75% yield based on recovered starting material)

Sources & evidence

ORD record
ord-ee27527e3149471697f0b565e4cf5d14
Source dataset
uspto-grants-2013_07
Patent number
US08491868B2

Reaction notes

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