布比卡因EP杂质B

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Under nitrogen atmosphere in a Parr bottle, 8.2 mmoles of [Cbz-piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] was dissolved in MeOH (100 mL). 10% Pd/C (0.5 g) was added, and the bottle was agitated under a hydrogen atmosphere (20 psi) for 30 minutes. The catalyst was filtered off using Millipore filter paper (washing with MeOH). The filtrate was concentrated to a thick syrup, yielding 1.75 grams (92% yield) of [piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] as an off-white solid. The product was characterized by NMR (DMSO). The catalyst was filtered off filter paper (washing with MeOH) The filtrate was concentrated to a thick syrup

反应条件: temp:0.00; pressure:0.00; stir:

实验步骤: 投料: 4.3　10：00　将原料SM1（6g，26mmol，1eq）加入反应瓶，乙酸（120ml），水（12ml）溶解，搅拌下加入亚硝酸钠（3.6g，52mmol，2eq），加入完毕室温反应 12：00　LCMS(175326-1-3) 没有原料剩余，主峰为产物峰 TLC(PE:EA=3:1) 有小极性新点生成，没有原料点 后处理　体系加水稀释（150ml），用乙酸乙酯（150*3）萃取，有机相用饱和食盐水洗，无水硫酸钠干燥，浓缩，得6.3g白色固体。

实验步骤: 投料: 4.2 12：00 1）将原料SM1（0.2g)加入反应瓶中，乙酸，水溶解，搅拌下加入亚硝酸钠，加入完毕室温反应 2）将原料SM1（0.２g）加入反应瓶中，THF溶解，加入亚硝酸叔丁酯，加入完毕室温反应 14：00　LCMS(175326-1-1) (175326-1-2) 1)没有原料剩余，主峰为产物峰。　2）没有反应

实验步骤: 投料: 在500ml 单口瓶中加入10g SM1、150ml ACN搅拌溶解后加入11.9g K2CO3、1.43g KI，再搅拌10min后滴加入9.4ml SM2升温至80℃搅拌反应过夜。\n监测: LCMS（148228-1-2-R）监测转化约40%，未反应完全，补加（1eq）SM2 4.7ml 继续反应。 2025-03-13 10:00 LCMS（148228-1-2-R-2）监测转化约60%，未反应完全，继续补加（1eq）SM2 4.7ml。 2025-03-14 09:30 LCMS（148228-1-2-R-3）监测转化约80%，停止反应。\n后处理: 反应液加入50ml DCM后超声过滤，用少量DCM洗涤滤饼后合并有机相浓缩，再用200ml DCM和200ml H2O萃取一次后收集有机相浓缩，旋干后加入40ml MeOH在45℃下加热超声溶解，再滴加4ml H2O后析出大量白色固体，用水润洗过滤后得到纯度达到95%的白色固体，固体再重复一次后冻干，刮下后得到5.55g白色粉末，送检HPLC纯度为97.504%。

实验步骤: 投料: 样品瓶中加入232mg SM1、276mg K2CO3、33mg KI、5ml ACN搅拌分散，后滴加入0.13ml SM2升温至60℃搅拌反应过夜。\n监测: LCMS（148228-1-1-R）监测未发现产物MS信号，升温至80℃反应。 2025-03-06 17:30 LCMS（148228-1-1-R-2）监测无明显变化。 怀疑氯代仲丁烷取代效果不佳，换成更易发生取代的溴代仲丁烷尝试，物料未到。\n监测: LCMS（148228-1-2-R）监测到产物MS，收率只有10~20%，怀疑是反应浓度不够的原因，开始放大生产。\n投料: 向反应液中加入0.3ml 溴代仲丁烷，80℃下搅拌反应过夜。

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

实验步骤: Under nitrogen atmosphere in a Parr bottle, 8.2 mmoles of [Cbz-piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] was dissolved in MeOH (100 mL). 10% Pd/C (0.5 g) was added, and the bottle was agitated under a hydrogen atmosphere (20 psi) for 30 minutes. The catalyst was filtered off using Millipore filter paper (washing with MeOH). The filtrate was concentrated to a thick syrup, yielding 1.75 grains (92% yield) of [piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] as an off-white solid. The product was characterized by NMR (DMSO). The catalyst was filtered off filter paper (washing with MeOH) The filtrate was concentrated to a thick syrup

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

实验步骤: Under nitrogen atmosphere in a Parr bottle, 8.2 mmoles of [Cbz-piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] was dissolved in MeOH (100 mL). 10% Pd/C (0.5 g) was added, and the bottle was agitated under a hydrogen atmosphere (20 psi) for 30 minutes. The catalyst was filtered off using Millipore filter paper (washing with MeOH). The filtrate was concentrated to a thick syrup, yielding 1.75 grams (92% yield) of [piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] as an off-white solid. The product was characterized by NMR (DMSO). The catalyst was filtered off filter paper (washing with MeOH) The filtrate was concentrated to a thick syrup

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

实验步骤: Under nitrogen atmosphere in a Parr bottle, 8.2 mmoles of [Cbz-piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] was dissolved in MeOH (100 mL). 10% Pd/C (0.5 g) was added, and the bottle was agitated under a hydrogen atmosphere (20 psi) for 30 minutes. The catalyst was filtered off using Millipore filter paper (washing with MeOH). The filtrate was concentrated to a thick syrup, yielding 1.75 grams (92% yield) of [piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] as an off-white solid. The product was characterized by NMR (DMSO). The catalyst was filtered off filter paper (washing with MeOH) The filtrate was concentrated to a thick syrup

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

实验步骤: Under nitrogen atmosphere in a Parr bottle, 8.2 mmoles of [Cbz-piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] was dissolved in MeOH (100 mL). 10% Pd/C (0.5 g) was added, and the bottle was agitated under a hydrogen atmosphere (20 psi) for 30 minutes. The catalyst was filtered off using Millipore filter paper (washing with MeOH). The filtrate was concentrated to a thick syrup, yielding 1.75 grams (92% yield) of [piperidine-2-carboxylic acid (2,6-dimethyl-phenyl)-amide] as an off-white solid. The product was characterized by NMR (DMSO). The catalyst was filtered off filter paper (washing with MeOH) The filtrate was concentrated to a thick syrup