Piperazine-2-carboxylic acid

Step 1: Intermediate 140: (+/-VI ^-bislfd .i-dimethylethvDoxyicarbonvD^-piperazinecarboxylic acid; In a 1 L round-bottomed flask 15.76 g of NaOH (394 mmole) were poured in 390 mL of 1, 4-di(tert-Butoxycarbonyl)3-carboxypiperazine (10gm, 49.2mm) was dissolved in 200ml of 50% methanol/water and the pH adjusted to 9.5 with 50% sodium hydroxide. Di-tert.butyldicarbonate (21 gm) was added and the pH kept at 9.5 with 1N sodium hydroxide. The reaction was monitored by tlc and more di-tert.butyldicarbonate added if needed. The reaction mixture was acidified with conc. Hydrochloric acid to pH=7 and then with citric acid to pH 3.8 and extracted with methylenechloride to obtain 15.4 gm of solid product.Synthesis of 4-(4-Chloro-3-methoxy-phenyl)-Intermediate 140: (+/-VI ^-bislfd .i-dimethylethvDoxyicarbonvD^-piperazinecarboxylic acid; In a 1 L round-bottomed flask 15.76 g of NaOH (394 mmole) were poured in 390 mL of 1, 4-di(tert-Butoxycarbonyl)3-carboxypiperazine (10gm, 49.2mm) was dissolved in 200ml of 50% methanol/water and the pH adjusted to 9.5 with 50% sodium hydroxide. Di-tert.butyldicarbonate (21 gm) was added and the pH kept at 9.5 with 1N sodium hydroxide. The reaction was monitored by tlc and more di-tert.butyldicarbonate added if needed. The reaction mixture was acidified with conc. Hydrochloric acid to pH=7 and then with citric acid to pH 3.8 and extracted with methylenechloride to obtain 15.4 gm of solid product.Synthesis of 4-(4-Chloro-3-methoxy-phenyl)-To a stirred suspension of Piperazine-2- carboxylic acid (20 g, 154 mmol) in a slurry with 200 mL of 1:1 H20/dioxane was cooled in an ice bath and treated with solid NaOH (11 g) followed by a solution of di-tert- butyl dicarbonate (21.6 g, 99 mmole) in dioxane added dropwise from an addition funnel. The reaction pH was adjusted to pH>10 as needed during the course of the reaction. The resulting mixture was allowed to stir for 3 h, then diluted with water until homogeneous and acidified with concentrated aqueous HCl until the pH was between 2 and 3. The solution was washed with ether then the pH was adjusted with NaOH until pH was 6.5 to 7. The solution was allowed to stand several days and the resulting precipitate was collected by filtration to give piperazine-1, 3-dicarboxylic acid 1-tert-butyl ester as a white solid (9.7 g) .A slurry of piperazine-1, 3-dicarboxylic acid 1-tert-butyl ester (4.62 g, 20.0 mmol) in CH3OH (100 mL) was treated with aqueous formaldehyde (40 mmol) and formic acid (70 mmol) , then heated at 65C for several hours. Upon completion by HPLC, the reaction was allowed to cool and was concentrated in vacuo. EPO

Piperazine-2-carboxylic acid is an important organic compound used as a basic structural component of pharmaceutical intermediates. Studies have shown that Piperazine-2-carboxylic acid derivatives are a potential multi-targeted ligands (MTDLs) anti-Alzheimer's disease (AD) active ingredient.

Molecular Weight:130.15
XLogP3:-3.5
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:130.074227566
Monoisotopic Mass:130.074227566
Topological Polar Surface Area:61.4
Heavy Atom Count:9
Complexity:116
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes