1-Ethylpiperazine → 4-(4-Ethyl piperazin-1-ylmethyl)-benzoic acid ethyl ester

HRID 336722Notes

Reaction equation

HRID 336722 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11]CBr)=[CH:7][CH:6]=1)[CH3:2].[CH2:15]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)[CH3:16]>C1COCC1.O>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:6]=[CH:7][C:8]([CH2:11][N:20]2[CH2:21][CH2:22][N:17]([CH2:15][CH3:16])[CH2:18][CH2:19]2)=[CH:9][CH:10]=1)[CH3:2]

Participants

5

Reactant 2

HCID 791961-EthylpiperazineHCID 12748305Ethyl 4-(2-bromoethyl)benzoate

Product 1

HCID 666608194-(4-Ethyl piperazin-1-ylmethyl)-benzoic acid ethyl esterYield 101.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromoethyl-benzoic acid ethyl ester (4.0 g, 16.46 mmol) in THF (30 mL), N-ethyl piperazine (3.76 g, 32.92 mmol) was added and the reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with water and the product was extracted with ethyl acetate. The combined organic layers were washed with water, brine, and dried over Na2SO4. The solvent was removed to give 4.61 g of crude 4-(4-ethyl piperazin-1-ylmethyl)-benzoic acid ethyl ester (100% yield). LAH (0.792 g, 20.86 mmol) was taken up in a 3-neck dry flask and THF (60 mL) was added on cooling. A solution of 4-(4-ethyl piperazin-1-ylmethyl)-benzoic acid ethyl ester (4.61 g, 16.69 mmol) in THF (10 mL) was added slowly on cooling. After completion of addition, the reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to 0° C., 10% NaOH solution was added, and then water was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine and dried over Na2SO4. The solvent was removed to give 2.78 g of crude (4-(4-ethyl piperazin-1-ylmethyl)phenyl)-methanol in 78% yield. To a 3-neck flask containing anhydrous CH2Cl2 (100 mL) cooled to the −78° C. oxalyl chloride (1.8 g, 14.25 mmol) and DMSO (1.85 g, 23.76 mmol) were added and the mixture was stirred for 15 min at −78° C. The solution of (4-(4-ethyl piperazin-1-ylmethyl)phenyl)-methanol (2.78 g, 11.88 mmol) in CH2Cl2 (10 mL) was added at −78° C. and stirred at −78° C. for 1 h. Then Et3N (4.8 g, 47.52 mmol) was added at −78° C. The reaction mixture was allowed to come to room temperature. Water was added and the organic layer was separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with water, brine and dried over Na2SO4. Then, solvent was removed to give crude 4-(4-ethyl piperazin-1-ylmethyl)benzaldehyde (2.5 g, 91%).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe combined organic layers were washed with water, brine
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed

Sources & evidence

ORD record
ord-acb353cfe3a94b5d99dfbe18819d062a
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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