2,6-Dimethylpiperazine → Ethyl 4-(3,5-dimethylpiperazin-1-yl)benzoate

HRID 1092034Notes

Reaction equation

HRID 1092034 reaction equation
[CH3:1][CH:2]1[CH2:7][NH:6][CH2:5][CH:4]([CH3:8])[NH:3]1.F[C:10]1[CH:20]=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][CH:11]=1>CS(C)=O>[CH3:8][CH:4]1[NH:3][CH:2]([CH3:1])[CH2:7][N:6]([C:10]2[CH:20]=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][CH:11]=2)[CH2:5]1

Participants

4

Reactant 2

HCID 660562,6-DimethylpiperazineHCID 67976Benzoic acid, 4-fluoro-, ethyl ester

Product 1

HCID 18425275Ethyl 4-(3,5-dimethylpiperazin-1-yl)benzoateYield 76%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

2,6-Dimethylpiperazine(3.43 g, 30.00 mmol) was added to ethyl 4-fluorobenzoate (1.101 mL, 7.5 mmol), in DMSO (10 mL) warmed to 120° C. under nitrogen. The resulting solution was stirred at 120° C. for 20 h. The reaction mixture was cooled and the solvent was evaporated. The crude product was purified by silica column chromatography, eluting with 10% methanol in dichloromethane containing 1% 0.880 ammonia. Pure fractions were evaporated to dryness to afford ethyl 4-(3,5-dimethylpiperazin-1-yl)benzoate (1.490 g, 76%) as a colourless solid. 1H NMR (399.9 MHz, CDCl3) δ 1.15 (6H, d), 1.37 (3H, t), 2.39 (1H, d), 2.42 (1H, d), 2.97-3.05 (2H, m), 3.65-3.69 (2H, m), 4.33 (2H, q), 6.84-6.87 (2H, m), 7.90-7.93 (2H, m)—NH not seen. MS: m/z=264 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent was evaporated
  3. customThe crude product was purified by silica column chromatography
  4. washeluting with 10% methanol in dichloromethane containing 1% 0.880 ammonia
  5. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-50c3548f516b452dbfbe988084a874c9
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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