4-甲氧基苯基乙酰胺

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

实验步骤: Title compound was prepared from [4-bromo-2-(2-bromoacetyl)phenoxy]acetic acid ethyl ester and 2-(4-methoxyphenyl)acetamide according to GP5 and GP3: LC/MS (an10p8) Rt 2.40 min, m/z 418 [M+H]+; 1H NMR (CDCl3): δ 3.72 (s, 3H), 4.14 (s, 1H), 4.85 (s, 1H), 6.92 (m, 2H), 7.02 (d, 1H), 7.2 (d, 1H), 7.23 (d, 1H), 7.44 (d, 1H), 8.05 (s, 1H), 8.67 (s, 1H), 13.2 (br s, 1H).

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

实验步骤: To a suspension of 4-methoxyphenylacetamide (5.06 g, 30.0 mmol) in toluene (10 mL) was added 2,6-di-t-butyl-4-hydroxytoluene (132 mg, 0.60 mmol) and chlorocarbonylsulfenyl chloride (5.52 mL, 60.0 mmol). The resulting mixture was warmed to 115° C. for 80 min during which time hydrochloric acid gas was evolved resulting in a yellow solution. To this solution additional chlorcarbonyl-sulfenylchloride (1.38 mL, 15.00 mmoles) was added and the mixture heated for 40 min and allowed to stand at room temperature overnight. The reaction mixture was cooled to 0° C. and stirred for 10 min before being filtered to remove a beige solid. The solid was washed with cold toluene (2×10 mL) and the filtrate was concentrated and purified by flash chromatography (silica gel, 20% ethyl acetate/hexanes) which afforded 5-(4-methoxy-benzyl)-[1,3,4]oxathiazol-2-one (1.12 g, 17%) as a yellow solid. was evolved resulting in a yellow solution the mixture heated for 40 min before being filtered to remove a beige solid The solid was washed with cold toluene (2×10 mL) the filtrate was concentrated purified by flash chromatography (silica gel, 20% ethyl acetate/hexanes) which

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

实验步骤: To a suspension of 4-methoxyphenylacetamide (5.06 g, 30.0 mmol) in toluene (10 mL) was added 2,6-di-t-butyl-4-hydroxytoluene (132 mg, 0.60 mmol) and chlorocarbonylsulfenyl chloride (5.52 mL, 60.0 mmol). The resulting mixture was warmed to 115° C. for 80 min during which time hydrochloric acid gas was evolved resulting in a yellow solution. To this solution additional chlorcarbonyl-sulfenylchloride (1.38 mL, 15.00 mmoles) was added and the mixture heated for 40 min and allowed to stand at room temperature overnight. The reaction mixture was cooled to 0° C. and stirred for 10 min before being filtered to remove a beige solid. The solid was washed with cold toluene (2×10 mL) and the filtrate was concentrated and purified by flash chromatography (silica gel, 20% ethyl acetate/hexanes) which afforded 5-(4-methoxy-benzyl)-[1,3,4]oxathiazol-2-one (1.12 g, 17%) as a yellow solid. was evolved resulting in a yellow solution the mixture heated for 40 min before being filtered to remove a beige solid The solid was washed with cold toluene (2×10 mL) the filtrate was concentrated purified by flash chromatography (silica gel, 20% ethyl acetate/hexanes) which

实验步骤: 02-08: 2.8 100ml三口瓶中称取SM1（990mg，6.0mmol，1.0eq.），置换氮气三次，加入超干THF（12ml，C=0.5M），固体不溶，冰水浴下缓慢滴加硼烷二甲硫醚（15ml，30mmol，5.0eq，C=2.0M）,15min滴完，60℃反应过夜。 2.9 TLC(DCM:MeOH=20:1)监测，能看到明显产物点，原料未反应完。LCMS监测，原料和产物一半一半，继续60℃反应。 2.10 TLC(DCM:MeOH=20:1)监测，原料点变浅，小杂点比昨天多了，LCMS监测，原料：产物=1：2左右，停止反应。冰水浴下，把反应液逐滴滴进甲醇中，滴完后自然恢复室温，搅拌至反应液中不再有气泡产生，此时硼烷二甲硫醚基本上淬灭完。旋干溶剂，得到透明油状物。透明油状物放-20℃冰箱保存。 2.13 透明油状物通过反相柱纯化，产物没有冲出来，且柱子越过越杂。 注：游离的胺不稳定，下次直接做成盐酸盐。

实验步骤: 01-31: 1.31 25ml双口瓶中称取SM1（165mg，1.0mmol，1.0eq.），置换氮气三次，加入超干THF（2ml，C=0.5M），固体不溶，冰水浴下缓慢滴加硼烷二甲硫醚（2.5ml，5.0mmol，5.0eq，C=2.0M）,15min滴完，然后恢复室温反应。 反应0.5h，TLC(DCM:MeOH=20:1)监测，没有新点，都是原料，继续室温反应。 反应1.5h，TLC(DCM:MeOH=20:1)监测，没有新点，都是原料，继续室温反应。 反应4.0h，TLC(DCM:MeOH=20:1)监测，有个很浅的新点（极性比SM1稍微小一点），LCMS监测，新点的分子量与产物一样。升至60℃反应。 反应6.0h，TLC(DCM:MeOH=20:1)监测，新点还是很浅，反应没有变杂，60℃过夜。 2.1 TLC(DCM:MeOH=20:1)监测，新点变浓，有一些很浅的小杂点，LCMS监测，反应稍微变杂了一点，大部分还是原料，继续60℃反应。 2.2 TLC(DCM:MeOH=20:1)监测，原料点变浅，小杂点比昨天多了，停止反应。冰水浴下，把反应液逐滴滴进甲醇中，滴完后自然恢复室温，搅拌至反应液中不再有气泡产生，此时硼烷二甲硫醚基本上淬灭完。旋干溶剂，得到透明油状物。透明油状物通过硅胶柱纯化，所有杂质点都冲出来产物点也没出来，用氨水把展开剂PH调至9-10再冲柱子，才冲出点东西来。LCMS对的上，量太少，核磁看不出来。

实验步骤: 01-29: 1.29 50ml双口瓶中称取SM1（165.19mg，1.0mmol，1.0eq.），置换氮气三次，加入超干THF（2ml，C=0.5M），固体微溶，室温下加入氢化铝锂（56.93mg，1.5mmol，1.5eq.），加完后室温反应。 反应1.5h，TLC（PE:EA=1:1）监测，没有新点，都是SM1。 反应4.0h，TLC（PE:EA=1:1）监测，有个很浅的新点，几乎都是SM1，升至60℃回流。 反应6.0h，TLC（PE:EA=1:1）监测，新点还是很浅，几乎都是SM1，60℃过夜。 1.30 TLC（PE:EA=1:1）监测，多了许多浅浅的杂点，几乎都是SM1，停止反应。

实验步骤: 01-13: 1.13 50ml双口瓶中称取SM1（165.19mg，1.0mmol，1.0eq.），置换氮气三次，加入超干THF（2ml，C=0.5M），固体微溶，室温下加入氢化铝锂（56.93mg，1.5mmol，1.5eq.），加完后室温反应。 反应0.5h，TLC（PE:EA=1:1）监测，没有新点，都是SM1。 反应1.5h，TLC（PE:EA=1:1）监测，没有新点，都是SM1。 反应4.0h，TLC（PE:EA=1:1）监测，有个很浅的新点，几乎都是SM1，室温过周末。 1.16 TLC（PE:EA=1:1）监测，新点还是很浅，几乎都是SM1，LCMS监测，能看到产物的MS，几乎都是SM1，升至60℃回流。 反应1.0h，TLC（PE:EA=1:1）监测，没有新点。 反应4.0h，TLC（PE:EA=1:1）监测，多了些杂点，原料点还是很浓，LCMS监测，反应变杂，基本上是原料。

实验步骤: 02-14: 2.14 100ml三口瓶中称取SM1（990mg，6.0mmol，1.0eq.），置换氮气三次，加入超干THF（12ml，C=0.5M），固体不溶，冰水浴下缓慢滴加硼烷二甲硫醚（15ml，30mmol，5.0eq，C=2.0M）,15min滴完，60℃反应过夜。 2.15 TLC(DCM:MeOH=20:1)监测，能看到明显产物点，原料未反应完。LCMS监测，原料和产物一半一半，继续60℃反应。 2.16 TLC(DCM:MeOH=20:1)监测，原料几乎反应完了，停止反应。冰水浴下，把反应液逐滴滴进甲醇中，滴完后自然恢复室温，搅拌至反应液中不再有气泡产生，此时硼烷二甲硫醚基本上淬灭完。旋干溶剂，得到透明油状物。透明油状物用甲醇溶解，用盐酸-二氧六环（4M）把溶液PH调至1-2，旋干，得到白色固体1g。

实验步骤: 02-06: 2.6 500ml单口瓶中称取对甲氧基苯乙酸（4.16g，25mmol，1.0eq.），加入超干DCM（50ml，C=0.5M），白色粉末溶解，室温下加入草酰氯（5.0ml，60mmol，2.4eq.），加完后，室温反应。 反应8.0h，TLC（PE:EA=4:1）监测，对甲氧基苯乙酸已反应完，冰水浴下，把氨水（17.05g，250mmol，10.0eq.）滴进反应液中（滴了25min），一边滴加一边有固体析出，加完后恢复室温过夜反应。 2.7 TLC（PE:EA=4:1）监测，酰氯已反应完，停止反应。反应液用水洗3次，每次200ml，洗三次，有机相干燥旋干，得到白色固体5g。

实验步骤: 01-10: 1.10 100ml单口瓶中称取对甲氧基苯乙酸（831mg，5.0mmol，1.0eq.），加入超干DCM（10ml，C=0.5M），白色粉末溶解，室温下加入草酰氯（0.5ml，6.0mmol，1.2eq.），加完后，室温反应。 反应0.5h，TLC（PE:EA=4:1）监测，有明显新点，对甲氧基苯乙酸很浓，继续室温反应。 反应1.0h，TLC（PE:EA=4:1）监测，对甲氧基苯乙酸未反应完，室温过夜。 1.11 TLC（PE:EA=4:1）监测，对甲氧基苯乙酸还是未反应完，补加草酰氯（0.42ml，5.0mmol，1.0eq），加完后继续室温反应。 反应3.5h，TLC（PE:EA=4:1）监测，对甲氧基苯乙酸已反应完，冰水浴下，把氨水（3.41g，50.0mmol，10.0eq.）滴进反应液中（滴了25min），一边滴加一边有固体析出，加完后恢复室温反应。 反应1.0h，TLC（PE:EA=4:1）监测，有明显新点（爬不起来），酰氯未反应完，LCMS监测，新点即为产物，继续室温搅拌。 反应2.5h，TLC（PE:EA=4:1）监测，酰氯未反应完，室温过夜。 1.12 TLC（PE:EA=4:1）监测，酰氯已反应完，停止反应。反应液水洗三次，每次50ml，有机相干燥旋干，得到白色固体520mg。

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

实验步骤: A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70%) of 2-(4-methoxyphenyl)acetamide as a white solid. The white solid forming was filtered dried under vacuum

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

实验步骤: A solution of 2-(4-methoxyphenyl)acetic acid (500 mg, 3.00 mmol) in DCM (30 ml) was added thionyl chloride (0.4 ml, 4.5 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and continued to stirred overnight. Then aqueous ammonia (2 ml) was added to the reaction mixture. The white solid forming was filtered and dried under vacuum to obtained 350 mg (70%) of 2-(4-methoxyphenyl)acetamide as a white solid. The white solid forming was filtered dried under vacuum