4-溴-2-碘苯甲酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

实验步骤: 投料: 取一个干燥的250mL三口瓶，加入 4-溴-2-碘苯甲酸甲酯（5.04g，14.67mmol，1eq）后，氮气保护3次（尽量做到无水无氧），再室温搅拌下加入超干四氢呋喃60mL(反应浓度0.25mol/L），随后将反应温度调至-65℃，在-65℃下缓慢滴加异丙基氯化镁-氯化锂（15mL，19.06mmol，1.3eq，1.3M inTHF)（滴加过程中会放热使温度上升，注意控制温度在-65℃以下），滴加完毕后使反应在-65℃下搅拌30分钟，30分钟后往上述反应液中缓慢滴加正戊醛（2.4mL，22mmol，1.5eq，ρ=0.81g/mL），随后反应自然回室温搅拌过夜。\n监测: 09:49 次日，GCMS：181363-1-2-OV（原料反应完，看到目标产物碎片峰268）（取样：反应液中加入氯化铵饱和溶液（淬灭异丙基氯化镁-氯化锂），再加入乙酸乙酯萃取，取上层送） TLC监测（PE:EA=50:1）：有与上一批次纯化出来一样的点。\n后处理: 在冰水浴条件下往反应液中加入氯化铵饱和溶液（淬灭异丙基氯化镁-氯化锂），再加入乙酸乙酯，然后将反应液中大部分的四氢呋喃减压浓缩除去，再用乙酸乙酯萃取（×3），收集有机相层，用无水硫酸钠干燥，过滤，收集滤液，旋干得到黄色粘稠物粗品（久置变固体）。\n纯化: 纯化。与上一批次的合并。柱层析。固定相为300-400目的硅胶，干法上样，流动相为PE（润柱）~（冲了一会没有紫外）~PE:EA=100:1（洗脱下杂质，再到产物）。（刚开始过出产物时，TLC是一个点，但收集旋干再TLC有三个点，一开始出产物时，前面几管注意辨别，注意收集干净产物；纯化时间较久，产物一直出不完），收集旋干得到浅橙色固体，送谱图：GCMS、HPLC和HNMR(CDCl3)，定量内标三甲氧基苯：96.32%。入库2.933g，浅橙色固体。收率：62%（两批次一共投6g来算）。

实验步骤: 投料: 取一个干燥的100mL三口瓶，加入 4-溴-2-碘苯甲酸甲酯（1g，2.93mmol，1eq）后，氮气保护3次（尽量做到无水无氧），再室温搅拌下加入超干四氢呋喃11.8mL(反应浓度0.25mol/L），随后将反应温度调至-65℃，在-65℃下缓慢滴加异丙基氯化镁-氯化锂（2.93mL，3.81mmol，1.3eq，1.3M inTHF)（滴加过程中会放热使温度上升，注意控制温度在-65℃以下），滴加完毕后使反应在-65℃下搅拌30分钟，30分钟后往上述反应液中缓慢滴加正戊醛（0.47mL，467.84mmol，1.5eq，ρ=0.81g/mL），随后反应自然回室温搅拌过夜。\n监测: 09:49 次日，TLC监测（PE:EA=10:1，原料像没反应，可能产物原料极性相近，展开剂极性没选好）。 10:00 GCMS：181363-1-1-OV（看到目标产物碎片峰268）（取样：反应液中加入氯化铵饱和溶液（淬灭异丙基氯化镁-氯化锂），再加入乙酸乙酯萃取，取上层送） 11:00 停止反应。\n后处理: 在冰水浴条件下往反应液中加入氯化铵饱和溶液（淬灭异丙基氯化镁-氯化锂），再加入乙酸乙酯，然后将反应液中大部分的四氢呋喃减压浓缩除去，再用乙酸乙酯萃取（×3），收集有机相层，用无水硫酸钠干燥，过滤，收集滤液，旋干得到黄色粘稠物粗品。\n纯化: 12.21 16:00 纯化。柱层析。固定相为300-400目的硅胶，干法上样，流动相为PE（润柱）~（冲了很久但是没有紫外）~（柱子放过夜第二天继续过） 12.22 09:10 继续纯化。流动相为PE（冲出有紫外的点：GCMS：181363-G1，不是产物）~PE:EA=50:1（冲下面有紫外的点，GCMS：181363-G2，有目标产物碎片峰，但不是很干净），收集选感情得到0.35g淡黄色固体。 \n纯化: 12.25 14:00 用甲基叔丁基醚打浆，但是全部溶清了，旋干得到黄色固体，与放大批次合并纯化。

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and copper cyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the title compound (2.39 g). The reaction mixture was cooled the mixture was extracted with ethyl acetate The organic layer was washed with a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution, and saturated brine The organic layer was dried over sodium sulfate the solvent was evaporated

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To methyl 2-amino-4-bromobenzoate (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. To this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5° C., 20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5° C. for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling the mixture was stirred at 5° C. for 2 hr cooling the mixture was extracted with ethyl acetate The organic layer was washed with 10% aqueous sodium sulfite solution added saturated brine and saturated brine dried over sodium sulfate the solvent was evaporated The obtained residue was purified by column chromatography (hexane:ethyl acetate)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 190 were added copper cyanide (1.16 g) and N-methylpyrrolidone (21 mL) and the mixture was stirred at 60° C. for 1 hr. Under cooling with water, ethyl acetate, saturated aqueous ammonium chloride solution and aqueous ammonia were added and the mixture was extracted with ethyl acetate. The organic layer was washed once with saturated aqueous ammonium chloride solution and aqueous ammonia, once with saturated aqueous ammonium chloride solution and once with saturated brine, and dried over sodium sulfate. The solvent was evaporated to give the title compound (2.39 g). were added the mixture was extracted with ethyl acetate The organic layer was washed once with saturated aqueous ammonium chloride solution and aqueous ammonia, once with saturated aqueous ammonium chloride solution and once with saturated brine dried over sodium sulfate The solvent was evaporated

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

实验步骤: To methyl 2-amino-4-bromobenzoate (5.75 g) was added ice-cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07 g) was added by small portions under ice-cooling and the mixture was stirred for 40 min. To this reaction mixture was added dropwise a solution obtained by dissolving potassium iodide (8.3 g) in water (25 mL) under ice-cooling, 20% sulfuric acid (30 mL) was added and the mixture was stirred for 2 hr. This reaction mixture was neutralized with 4N aqueous sodium hydroxide solution under ice-cooling, and the mixture was extracted with ethyl acetate, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride. The organic layer was washed once with saturated brine and 10% aqueous sodium sulfite solution, with saturated brine, and dried over sodium sulfate. The solvent was evaporated and the residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (7.05 g). was added by small portions under ice- cooling To this reaction mixture was added dropwise a solution obtained cooling the mixture was stirred for 2 hr cooling the mixture was extracted with ethyl acetate, 10% aqueous sodium sulfite solution (45 mL) and sodium chloride The organic layer was washed once with saturated brine and 10% aqueous sodium sulfite solution, with saturated brine dried over sodium sulfate The solvent was evaporated the residue was purified by column chromatography (hexane:ethyl acetate)