2-(4-溴苯基)丙酸甲酯

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

实验步骤: To a stirred solution of compound 68b (5 g, 0.02 mol) in THF (100 mL) was added a 1 M THF solution of NaHMDS (22.6 mL, 22.6 mmol) at 0° C. under a nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was then cooled to 0° C. and iodomethane (3.19 g, 22.5 mmol) was added dropwise. The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction mixture was then treated with water (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68c as brown oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C11H13BrO2: 256.0 (M). found: 256.0. The reaction mixture was then cooled to 0° C. The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction mixture was then treated with water (50 mL) extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

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

实验步骤: To a stirred solution of compound 68b (5 g, 0.02 mol) in THF (100 mL) was added a 1 M THF solution of NaHMDS (22.6 mL, 22.6 mmol) at 0° C. under a nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was then cooled to 0° C. and iodomethane (3.19 g, 22.5 mmol) was added dropwise. The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction mixture was then treated with water (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68c as brown oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C11H13BrO2: 256.0 (M). found: 256.0. The reaction mixture was then cooled to 0° C. The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction mixture was then treated with water (50 mL) extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

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

实验步骤: To a stirred solution of compound 68a (7.5 g, 0.032 mol) in THF (100 mL), 1 M THF solution of NaHMDS (36 mL, 0.036 mol) was added dropwise at 0 C. The resulting solution was allowed to warm to room temperature and stirred for 1 h before cooling back down to 0° C. The cooled reaction mixture was treated dropwise with iodomethane (5.1 g, 0.035 mol). The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction was then quenched by the addition of water (50 mL). The reaction mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68b as a yellow oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C10H11BrO2: 242.0 (M). found: 242.0. before cooling back down to 0° C The cooled reaction mixture The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction was then quenched by the addition of water (50 mL) The reaction mixture was extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

实验步骤: 投料: 3 L三口瓶中加入碳酸钠（27.35 g，258 mmol，2.0 eq），加入四三苯基膦钯（7.45 g，6.45 mmol，0.05 eq），加入环己烯-1-基硼酸（100 g，258 mmol，2.0 eq），加完后置换氮气三次，后加入原料（31.36 g，129 mmol，1.0 eq），后加入516 ml甲苯和129 ml纯水溶解，后升温至100°回流搅拌过夜，体系呈黑色\n监测: GCMS（EA）：148832-2，反应完全\n后处理: 铺硅藻土过滤，乙酸乙酯冲洗滤饼，旋掉大部分滤液，后加入EA和水萃取分液，有机相干燥浓缩，得橙黄色固液混合物\n纯化: 柱层析纯化（PE：EA=80:1），收集干净产物得黄色液体25.26 g，收率80%，HNMR（DMSO）：148832-2，结构正确，同时收集含杂质产物9.26 g

实验步骤: 投料: 500 ml双口瓶中加入碳酸钠（5.51 g，52 mmol，2.0 eq），加入四三苯基膦钯（1.5 g，1.3 mmol，0.05 eq），加入环己烯-1-基硼酸（20.17 g，52 mmol，2.0 eq），加完后置换氮气三次，后加入原料（6.32 g，26 mmol，1.0 eq），后加入104 ml甲苯和26 ml纯水溶解，后升温至100°回流搅拌过夜，体系呈黑色\n监测: GCMS（EA）：148832-2，反应完全\n后处理: 铺硅藻土过滤，乙酸乙酯冲洗滤饼，旋掉大部分滤液，后加入EA和水萃取分液，有机相干燥浓缩，得到黑色油状物\n纯化: 柱层析纯化（PE：EA=80:1），收集干净产物得黄色液体3.47 g，HNMR（DMSO）：C4X-148832-2，结构正确，同时收集含杂质产物1.48 g

实验步骤: 投料: 往3 L三口瓶中加入原料4-溴苯乙酸甲酯（49.1 g，214 mmol，1.0 eq），加入713 ml超干THF，置换氮气三次，呈无色透明，在-78℃下使用滴液漏斗滴加LDA （117.5 ml，1.1eq），[2M in THF]，体系呈黄色透明，加完后保持-78°搅拌1h，使用THF润洗滴液漏斗，后滴加碘甲烷（13.3 ml，1.0 eq），回至室温反应，体系由黄色变为橙色最后为橙红色\n监测: TLC（PE：EA=10:1），反应完全\n后处理: 往反应液中加入饱和氯化铵溶液淬灭，水相出现白色浑浊，分液，EA萃取水相，合并有机相，干燥浓缩，得到固液混合物\n纯化: 柱层析纯化（PE：EA=15:1），收集产物得橙红色液体44.06 g，收率84.7%，产物带有原料中的杂质，分离不开，2-24 HNMR（DMSO）：148832-1

实验步骤: 投料: 100 ml双口瓶中加入碳酸钠（1.23 g，11.6 mmol，2.0 eq），四三苯基膦钯（335 mg，0.29 mmol，0.05 eq），加入环己烯-1-基硼酸（4.5 g ，11.6 mmol，2.0 eq），加完后置换氮气三次，后加入原料（1.4 g，5.8 mmol，1.0 eq），后加入24 ml甲苯和6 ml纯水溶解，后升温至100°回流搅拌过夜。\n监测: TLC（PE：EA=15:1），原料与产物点极性相近，无法确定原料是否消耗完，跑大板，2-22 HNMR（DMSO）：148832-2，结构为产物\n后处理: 铺硅藻土过滤，乙酸乙酯冲洗滤饼，旋掉大部分滤液，后加入EA和水萃取分液，有机相干燥浓缩，得灰色固体

实验步骤: 投料: 往100ml三口瓶中加入原料4-溴苯乙酸甲酯（2.21 g，9.6 mmol，1.0 eq），加入32 ml超干THF，置换氮气三次，在-78℃下滴加LDA （5.28 ml，1.1 eq），[2M in THF]，体系呈黄色澄清，加完后保持-78℃搅拌1 h，后滴加碘甲烷（0.6 ml，1.0 eq），后回至室温反应，体系逐渐变为橙色，最后为棕色\n监测: TLC（PE：EA=10:1），原料上方自带一个杂点\n后处理: 往反应液中加入饱和氯化铵溶液淬灭，分液，EA萃取水相，合并有机相，干燥浓缩，得到黄色固液混合物\n纯化: 柱层析纯化（PE：EA=15:1），产物迅速冲出，收集干净产物得黄色液体1.4 g，收率60%，另收集含杂质产物1.27 g，GCMS（EA）：C4X-148832-1，HNMR（DMSO）：C4X-148832-1，结构和分子量正确

实验步骤: 投料: 250ml双口瓶中加入碳酸钠（3.64g，2.0eq），加入四三苯基膦钯（0.993mg，0.05eq），加入环己烯-1-基硼酸（4.33g，2.0eq），加完后置换氮气三次，后加入原料（4.18g，1.0eq），后加入68ml甲苯和17ml纯水溶解，后升温至100°回流搅拌过夜。\n后处理: 停止加热搅拌，铺硅藻土过滤，乙酸乙酯冲洗滤饼，旋掉大部分滤液，后加入EA和水萃取分液，有机相干燥浓缩，得到黑色油状物。\n监测: 送GCMS，C4X-148832-2-2-S1，原料反应完全，停止反应。\n纯化: 过柱，将黑色油状物用DCM溶解，拌样，手动过柱，流动相PE：EA=80:1,收集干净的有产物的流动相，旋干，得到无色油状物2.46g，送HNMR，C4X-148832-2-2-C1，确认结构正确。收率59%

实验步骤: 投料: 往50ml双口瓶中加入碳酸钠（436mg，2.0eq），加入四三苯基膦钯（119mg，0.05eq），加入 环己烯-1-基硼酸（518mg，2.0eq），加完后置换氮气三次，后加入原料（500mg，1.0eq），后加入10ml甲苯和2ml纯水溶解，后升温至100°回流搅拌过夜。\n监测: 取样TLC监测，点板分不开，送GCMS，C4X-148832-2-1-S1，原料反应完全，停止反应。\n后处理: 停止加热搅拌，铺硅藻土过滤，乙酸乙酯冲洗滤饼，旋掉大部分滤液，后加入EA和水萃取分液，有机相干燥浓缩，得到黑色油状物。\n纯化: 过柱，将黑色油状物用DCM溶解，拌样，手动过柱，流动相PE：EA50:1,分别收集过干净的点送GCMS，确认产物点，后将有产物的流动相旋干，得到无色油状物260mg，送HNMR，C4X-148832-2-1-C1，确认结构正确。

实验步骤: 投料: 往250ml三口瓶中加入原料4-溴苯乙酸甲酯（5g，1.0eq），置换氮气三次，加入72ml超干THF，在-78℃下滴加LDA （12ml，1.1eq），[2M in THF]，加完后保持-78°搅拌1h，后滴加碘甲烷（1.36ml，1.0eq），后回至室温反应。\n监测: 反应1.5h，TLC监测，PE：EA=10:1，原料反应完全，停止反应。 送GCMS，C4X-148832-1-1-S1，看到有产物分子量，和原料分子量，比例1:1,。\n后处理: 往反应液中加入饱和氯化铵溶液淬灭，分液，EA萃取水相，合并有机相，干燥浓缩，得到黄色固液混合物。\n纯化: 拌样过柱，手动柱，100-200目硅胶，流动相，PE：EA=15:1，产物迅速冲出，旋干送HNMR和GCMS，C4X-148832-1-1-C1，HNMR确认是目标产物，可能有少许原料，GCMS不作为参考依据。旋干得到4.68g，收率88%

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-(4-bromophenyl)propanoate, 7-e, (500 mg, 2.06 mmol), diethylphosphite (994 mg, 7.20 mmol) and triethylamine (681 mg, 6.7 mmol) in toluene (5 mL) was added [1,1′-bis(diphenylphosphino) ferrocene]dicholoropalladium (54 mg). The resulting reaction mixture was heated at 110° C. under nitrogen overnight. The cooled reaction mixture was filtrated (washed with DCM, 3×10 mL), and the filtrate was concentrated to afford the crude product which was purified by column chromatography to give the title compound, 7-f, as yellow brown oil (500 mg, 99%). 1H NMR (300 MHz, CDCl3) δ1.30-1.39 (m, 6H), 1.51 (d, J=7.2 Hz, 3H), 3.67 (s, 3H), 3.77 (q, J=7.2 Hz, 1H), 4.05-4.20 (m, 4H), 7.37-7.41 (m, 2H), 7.72-7.79 (m, 2H). LC-MS (M+H)+ 301. The resulting reaction mixture The cooled reaction mixture was filtrated (washed with DCM, 3×10 mL) the filtrate was concentrated to afford the crude product which was purified by column chromatography