N-Boc-piperazine-2-carboxylic acid methyl ester

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro phenyl boronic acid (2.0 equiv, 3.68 mmol) and piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 equiv, 1.84 mmol) were dissolved in dichloromethane followed by the addition of copper acetate (1.0 equiv), 4 Å molecular sieves and pyridine (2.0 equiv). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%). The reaction mixture was concentrated in vacuo dissolved in ethyl acetate filtered through celite concentrated The crude product was purified elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro phenyl boronic acid (2.0 equiv, 3.68 mmol) and piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 equiv, 1.84 mmol) were dissolved in dichloromethane followed by the addition of copper acetate (1.0 equiv), 4 Å molecular sieves and pyridine (2.0 equiv). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%). The reaction mixture was concentrated in vacuo dissolved in ethyl acetate filtered through celite concentrated The crude product was purified elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazine-1,2,4-tricarboxylic acid 1-tert-butyl ester 4-(9H-fluoren-9-ylmethyl) ester 2-methyl ester (2.03 mmol) in DMF (4.0 mL) was added diethylamine (5%) and the resulting solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified using ethyl acetate/methanol (10%). ESI-MS m/z: 245(M+1), UV retention time: 0.78 min. The reaction mixture was concentrated in vacuo purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazine-1,2,4-tricarboxylic acid 1-tert-butyl ester 4-(9H-fluoren-9-ylmethyl) ester 2-methyl ester (2.03 mmol) in DMF (4.0 mL) was added diethylamine (5%) and the resulting solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified using ethyl acetate/methanol (10%). ESI-MS m/z: 245(M+1), UV retention time: 0.78 min. The reaction mixture was concentrated in vacuo purified

反応条件: temp:71.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a dry 100 ml one necked round bottom flask equipped with a stirring bar was added 1-tert-butyl 2-methyl piperazine-1,2-dicarboxylate (5 g, 20.5 mmol) under N2 (FIG. 1). Anhydrous acetonitrile (60 mL) was added followed by the additions of BnBr (2.7 mL, 22.5 mmol) and triethylamine (8.5 ml, 61.5 mmol). A condenser was then put on to the flask and the reaction mixture was heated at 71° C. for 45 minutes. The reaction mixture was allowed to come to room temperature and concentrated under reduced pressure. It was then diluted with dichloromethane and washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was purified with flash column (PE: EA=8:1) to yield 4.5 g (66%) of 111a. MS: [M+H]+: 335 A condenser was then put on to the flask to come to room temperature concentrated under reduced pressure It was then diluted with dichloromethane washed with water and brine The organic layer was dried over Na2SO4 filtered concentrated under reduced pressure The crude compound was purified with flash column (PE: EA=8:1)

反応条件: temp:71.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a dry 100 ml one necked round bottom flask equipped with a stirring bar was added 1-tert-butyl 2-methyl piperazine-1,2-dicarboxylate (5 g, 20.5 mmol) under N2 (FIG. 1). Anhydrous acetonitrile (60 mL) was added followed by the additions of BnBr (2.7 mL, 22.5 mmol) and triethylamine (8.5 ml, 61.5 mmol). A condenser was then put on to the flask and the reaction mixture was heated at 71° C. for 45 minutes. The reaction mixture was allowed to come to room temperature and concentrated under reduced pressure. It was then diluted with dichloromethane and washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was purified with flash column (PE: EA=8:1) to yield 4.5 g (66%) of 111a. MS: [M+H]+: 335 A condenser was then put on to the flask to come to room temperature concentrated under reduced pressure It was then diluted with dichloromethane washed with water and brine The organic layer was dried over Na2SO4 filtered concentrated under reduced pressure The crude compound was purified with flash column (PE: EA=8:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro phenyl boronic acid (2.0 equiv, 3.68 mmol) and piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 equiv, 1.84 mmol) were dissolved in dichloromethane followed by the addition of copper acetate (1.0 equiv), 4 Å molecular sieves and pyridine (2.0 equiv). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%). ESI-MS m/z: 354 (M+1), UV retention time: 2.88 min. Reference: Tetrahedron Letters, 2001, 42, 3415–3418. The reaction mixture was concentrated in vacuo dissolved in ethyl acetate filtered through celite concentrated The crude product was purified elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazine-1,2,4-tricarboxylic acid 1-tert-butyl ester 4-(9H-fluoren-9-ylmethyl)ester 2-methyl ester (2.03 mmol) in DMF (4.0 mL) was added diethylamine (5%) and the resulting solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified using ethyl acetate/methanol (10%). ESI-MS m/z: 245(M+1), UV retention time: 0.78 min. The reaction mixture was concentrated in vacuo purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro phenyl boronic acid (2.0 equiv, 3.68 mmol) and piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 equiv, 1.84 mmol) were dissolved in dichloromethane followed by the addition of copper acetate (1.0 equiv), 4 Å molecular sieves and pyridine (2.0 equiv). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%). ESI-MS m/z: 354 (M+1), UV retention time: 2.88 min. The reaction mixture was concentrated in vacuo dissolved in ethyl acetate filtered through celite concentrated The crude product was purified elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of piperazine-1,2,4-tricarboxylic acid 1-tert-butyl ester 4-(9H-fluoren-9-ylmethyl) ester 2-methyl ester (2.03 mmol) in DMF (4.0 mL) was added diethylamine (5%) and the resulting solution was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified using ethyl acetate/methanol (10%). ESI-MS m/z: 245 (M+1), UV retention time: 0.78 min. The reaction mixture was concentrated in vacuo purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro phenyl boronic acid (2.0 equiv, 3.68 mmol) and piperazine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 equiv, 1.84 mmol) were dissolved in dichloromethane followed by the addition of copper acetate (1.0 equiv), 4 Å molecular sieves and pyridine (2.0 equiv). The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%). ESI-MS m/z: 354 (M+1), UV retention time: 2.88 min. The reaction mixture was concentrated in vacuo dissolved in ethyl acetate filtered through celite concentrated The crude product was purified elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (20%)