4-氧代-1,2-哌啶二羧酸1-叔丁酯2-甲酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.1 g, 3.9 mmol) in 20 mL of methanol was added sodium borohydride (0.14 9, 3.9 mmol) at 0° C. After stirring for 2 h at 0° C., the mixture was diluted with ethyl acetate, washed with 1M HCl, 1M NaOH, and brine, dried over Na2SO4, filtered and concentrated. The residue was taken up in 10 mL of 6M aqueous HCl and was refluxed for 4 h. After cooling to room temperature, the mixture was concentrated in vacuo, and the residue was dissolved in 5.5 mL of anhydrous DMF. The solution was cooled to 0° C. and was treated with triethylamine (4.8 mL, 34 mmol) and 4-benzyloxy-benzenesulfonyl chloride (2.5 g, 8.8 mmol). After stirring for 2 h, the mixture was diluted with 1M HCl, extracted 3× with ethyl acetate, and the organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane, affording 0.43 g of 5-(4-benzyloxy-benzenesulfonyl)-2-oxa-5-aza-bicyclo[2.2.2]octan-3one as a colorless solid. washed with 1M HCl, 1M NaOH, and brine dried over Na2SO4 filtered concentrated was refluxed for 4 h After cooling to room temperature the mixture was concentrated in vacuo the residue was dissolved in 5.5 mL of anhydrous DMF The solution was cooled to 0° C. After stirring for 2 h extracted 3× with ethyl acetate the organic layers were dried over Na2SO4 filtered concentrated in vacuo The residue was filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a refluxing mixture of rhodium acetate dimer (0.0093 g, 0.02 mmol) and 40 mL of benzene was added dropwise a solution of 2-tert-butoxycarbonylamino-5-diazo-4-oxo-pentanoic acid methyl ester (0.60 g, 2.1 mmol) in 4.5 mL of benzene. After stirring for 2 h at reflux, the mixture was cooled to room temperature, concentrated in vacuo, and filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane. Concentration of the filtrate afforded 0.53 g of 4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester as a yellow oil. at reflux concentrated in vacuo filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a refluxing mixture of rhodium acetate dimer (0.0093 g, 0.02 mmol) and 40 mL of benzene was added dropwise a solution of 2-tert-butoxycarbonylamino-5-diazo-4-oxo-pentanoic acid methyl ester (0.60 g, 2.1 mmol) in 4.5 mL of benzene. After stirring for 2 h at reflux, the mixture was cooled to room temperature, concentrated in vacuo, and filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane. Concentration of the filtrate afforded 0.53 g of 4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester as a yellow oil. at reflux concentrated in vacuo filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a refluxing mixture of rhodium acetate dimer (0.0093 g, 0.02 mmol) and 40 mL of benzene was added dropwise a solution of 2-tert-butoxycarbonylamino-5-diazo-4-oxo-pentanoic acid methyl ester (0.60 g, 2.1 mmol) in 4.5 mL of benzene. After stirring for 2 h at reflux, the mixture was cooled to room temperature, concentrated in vacuo, and filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane. Concentration of the filtrate afforded 0.53 g of 4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester as a yellow oil. at reflux concentrated in vacuo filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of oxalyl chloride ((15 mL, 30 mmol, 2 M dichloromethane) in CH2Cl2 (100 mL) cooled to −78° C. was added DMSO (4.5 mL, 63.4 mmol). The mixture was stirred at this temperature for 1 h, after which 4-hydroxy-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (2.0 g, 7.71 mmol dissolved in CH2Cl2) as added. The mixture stirred for a further 1 h and Et3N (20 mL) was then added and the mixture stirred for another 30 min. The mixture was then allowed to warm to −40° C. and poured into a solution of 10% NaHSO4. The reaction mixture was then extracted with ethyl acetate. The organic extract was then washed with brine and dried over MgSO4 (anhydrous) and the solvent was removed in vacuo and the crude residue was purified by silica gel flash column chromatography giving 1.75 g (88%) of the product as a yellow oil. 1H-NMR (CDCl3), δ(ppm): 4.85 (br, d, 1H), 4.02 (m, 1H), 3.61 (s, 3H), 3.58 (br, 1H), 2.75 (m, 2H), 2.44 (br, 2H), 1.43 (br, s, 9H). The mixture stirred for a further 1 h the mixture stirred for another 30 min to warm to −40° C. The reaction mixture was then extracted with ethyl acetate The organic extract was then washed with brine dried over MgSO4 (anhydrous) the solvent was removed in vacuo the crude residue was purified by silica gel flash column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02–4.11 (m, 1), 3.73 (s, 3), 3.67–3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (2S)-4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.52 g, 2.15 mmol) in methanol (10 mL), 2 M solution of TMS-diazomethane (2 mL, 4 mmol) in hexane was added and stirred at room temperature for 15 min. The reaction solvent was removed and the methyl ester product obtained (4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester) was used as such for the next reaction (0.55 g, 100%): MS (ESPOS): 258 [M+H]+; 1H NMR (300 MHz, CD3OD) δ 5.13, 4.86 (bs, 1), 4.02-4.11 (m, 1), 3.73 (s, 3), 3.67-3.72 (m, 1), 2.78 (d, J=4.2 Hz, 2), 2.51 (bs, 2), 1.46 (bs, 9). The reaction solvent was removed