4-(4-Methyl-1-piperazinylmethyl)benzoic acid

General procedure: AcOH (100percent) (140 mL, 2.44 ml) was added over 1 h to a flask containing stirred NaBHA suspension of 4-formylbenzoic acid (10.0 g, 67 mmol) in methanol (100 ml) is treated sequentially with 1-methylpiperazine (7.3 g, 73 mmol) and platinum (5percent) on sulfided carbon (1 g). The resulting suspension is then heated at 80° C. and is subjected to a pressure of 5 bar of hydrogen for a period of 20 hrs until the hydrogen uptake is complete. The reaction mixture is cooled to room temperature and filtrated over a pad of Celite. Water (20 ml) is used to rinse the reactor and dissolve the fraction of 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid that crystallizes on the walls during the cooling of the reaction mixture. The resulting aqueous solution is filtrated over the pad of Celite employed previously. The combined filtrates are concentrated in vacuo and crystallized in EtOH/H2O 9:1 v/v to give 10.9 g (70percent) of 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid as colorless crystals.General procedure: General procedure for saponification: Ester derivative was dissolved in THF (0.8 mol/L) and a water solution of LiOH (3 eq) was added. Mixture was heated to reflux for 4 h. THF was evaporated and impurities were extracted with EtOAc at pH = 12. Aqueous layer was saturated with NaClGeneral procedure: General procedure for saponification: Ester derivative was dissolved in THF (0.8 mol/L) and a water solution of LiOH (3 eq) was added. Mixture was heated to reflux for 4 h. THF was evaporated and impurities were extracted with EtOAc at pH = 12. Aqueous layer was saturated with NaClExample 5 Example 1350 ml of ethanol was added to 155 g (1.547 mol) of N-methylpiperazine. At room temperature (25+/-3° C.), 60 g (0.351 mol) of 4-chloromethylbenzoic acid was added thereto and stirred for 6-7 hours. The reaction was analyzed by HPLC, and then the reaction solution was distilled under reduced pressure to remove ethanol, and 60 ml of 1-butanol was added thereto. The mixture was azeotropically distilled at 70+/-2° C. and concentrated to produce a solid. 600 ml of 2-propanol was added thereto and the mixture was stirred at room temperature (25+/-3° C.) for 30 minutes, stirred under reflux for 15 minutes, and then stirred at room temperature (25+/-3° C.) for 12 hours with slow cooling. The produced precipitate was cooled to 19+/-3° C., stirred for 1 hour and then filtered. The filtrate was washed with 50 ml of cooled 2-propanol and dried in an oven at 60° C., thereby obtaining a white compound of formula (2) (60 g, yield: 72percent, purity: 95percent or higher).HPLC purity: 99.123percent (desmethyl impurity: 0.042percent, starting material 0.42percent).Thin layer chromatography: Methanol-Dichloromethane (7:5), Rf: 0.2.HCL-SALT OF 4- (4-METHYLPIPERAZIN-1-YLMETHYL) benzoic acid methyl ester (1.25 g) was dissolved in potassium hydroxide-methanol solution (0.93 g KOH in 15 ml methanol). Water (0.75 ml) was added and the mixture was refluxed for 1 hour. The reaction mixture was allowed to cool into room temperature and the pH was tuned to 6 with 2 M HC1. The solvent was evaporated and the residue was dried under vacuum. The residue contained 4- (4-METHYLPIPERAZIN-1-YLMETHYL) benzoic acid and inorganic salts. It was used further without purification and the yield of title compound was assumed to be 100percent. 1H NMR (400 MHz, d6-DMSO) 8 : 2.27 (s, 3H), 2.44 (bs, 2H), 3.18-3. 95 (m, 8H), 7.41 (d, 2H, J 8. 0 Hz), 7.89 (d, 2H, J 8. 1 Hz).

Molecular Weight:234.29
XLogP3:-1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:234.136827821
Monoisotopic Mass:234.136827821
Topological Polar Surface Area:43.8
Heavy Atom Count:17
Complexity:254
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes