3,4-吡咯二羧酸二乙酯

反应条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diethyl pyrrole-3,4-dicarboxylate (39 g, 0.185 mol) in THF (1600 mL) was treated with NaH (60%, 7.6 g, 0.19 mol). The reaction mixture was heated to reflux for 1 hour. The reaction was then cooled to 30° C. and N-(3-bromopropyl)phthalimide (52 g, 0.19 mol) was added. The reaction mixture was heated to reflux for 1 hour, cooled, filtered, and concentrated in vacuo. The resultant gum was partitioned between ETOAC/H2O and extracted with EtOAC (2×300 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was recrystallized from EtOAC to give the title compound 68 g (92%) (mp 100-101° C.). 1H NMR (DMSO) δ1.24 (t, 3H, CH), 2.06 (m, 2H, CH3), 3.57 (t, 2H, CH2), 4.14 (m, 4H, CH2), 7.49 (s, 2H, ArH), 7.86 (m, 4H, ArH). The reaction mixture was heated to reflux for 1 hour The reaction mixture was heated to reflux for 1 hour cooled filtered concentrated in vacuo The resultant gum was partitioned between ETOAC/H2O extracted with EtOAC (2×300 mL) The organic layer was dried (MgSO4) filtered concentrated in vacuo The resultant solid was recrystallized from EtOAC

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

实验步骤: Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL, 50 mmol) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2×250 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1H NMR (DMSO) δ1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH). the mixture was extracted with THF (2×250 mL) The organic layers were dried (Na2SO4) filtered concentrated in vacuo to give a solid The solid was recrystallized from MeOH

反应条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diethyl pyrrole-3,4-dicarboxylate (39 g, 0.185 mol) in THF (1600 mL) was treated with NaH (60%, 7.6 g, 0.19 mol). The reaction mixture was heated to reflux for 1 hour. The reaction was then cooled to 30° C. and N-(3-bromopropyl)phthalimide (52 g, 0.19 mol) was added. The reaction mixture was heated to reflux for 1 hour, cooled, filtered, and concentrated in vacuo. The resultant gum was partitioned between ETOAC/H2O and extracted with EtOAC (2×300 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was recrystallized from EtOAC to give the title compound 68 g (92%) (mp 100-101° C). 1H NMR (DMSO) δ 1.24 (t, 3H, CH), 2.06 (m, 2H, CH3), 3.57 (t, 2H, CH2), 4.14 (m, 4H, CH2), 7.49 (s, 2H, ArH), 7.86 (m, 4H, ArH). The reaction mixture was heated to reflux for 1 hour The reaction mixture was heated to reflux for 1 hour cooled filtered concentrated in vacuo The resultant gum was partitioned between ETOAC/H2O extracted with EtOAC (2×300 mL) The organic layer was dried (MgSO4) filtered concentrated in vacuo The resultant solid was recrystallized from EtOAC

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

实验步骤: Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL. 50 mmol.) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2×250 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1H NMR (DMSO) δ 1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH) the mixture was extracted with THF (2×250 mL) The organic layers were dried (Na2SO4) filtered concentrated in vacuo to give a solid The solid was recrystallized from MeOH

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

实验步骤: Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL. 50 mmol.) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2×250 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1H NMR (DMSO) δ 1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH) the mixture was extracted with THF (2×250 mL) The organic layers were dried (Na2SO4) filtered concentrated in vacuo to give a solid The solid was recrystallized from MeOH

反应条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diethyl pyrrole-3,4-dicarboxylate (39 g, 0.185 mol) in THF (1600 mL) was treated with NaH (60%, 7.6 g, 0.19 mol). The reaction mixture was heated to reflux for 1 hour. The reaction was then cooled to 30° C. and N-(3-bromopropyl)phthalimide (52 g, 0.19 mol) was added. The reaction mixture was heated to reflux for 1 hour, cooled, filtered, and concentrated in vacuo. The resultant gum was partitioned between ETOAC/H2O and extracted with EtOAC (2×300 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was recrystallized from EtOAC to give the title compound 68 g (92%) (mp 100-101° C.). 1H NMR (DMSO) δ1.24 (t, 3H, CH), 2.06 (m, 2H, CH3), 3.57 (t, 2H, CH2), 4.14 (m, 4H, CH2), 7.49 (s, 2H, ArH), 7.86 (m, 4H, ArH). The reaction mixture was heated to reflux for 1 hour The reaction mixture was heated to reflux for 1 hour cooled filtered concentrated in vacuo The resultant gum was partitioned between ETOAC/H2O extracted with EtOAC (2×300 mL) The organic layer was dried (MgSO4) filtered concentrated in vacuo The resultant solid was recrystallized from EtOAC

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

实验步骤: Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL, 50 mmol) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2×250 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1H NMR (DMSO) δ1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH). the mixture was extracted with THF (2×250 mL) The organic layers were dried (Na2SO4) filtered concentrated in vacuo to give a solid The solid was recrystallized from MeOH

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

实验步骤: Tosylmethyl isocyanide (9.8 g, 50 mmol), diethyl fumarate (8.2 mL, 50 mmol) and dry THF (1000 mL) were added dropwise to a stirred suspension of potassium t-butoxide (11.2 g, 100 mmol) and THF (150 mL). The mixture was stirred for 2 hours, saturated NaCl (500 mL) was added, and the mixture was extracted with THF (2×250 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo to give a solid. The solid was recrystallized from MeOH to give the title compound 4.6 g (44%) (mp 148-149° C.). 1H NMR (DMSO) δ1.22 (t, 3H, CH3), 4.18 (q, 2H, CH2), 7.39 (s, 2H, ArH), 11.8 (bs, 1H, NH). the mixture was extracted with THF (2×250 mL) The organic layers were dried (Na2SO4) filtered concentrated in vacuo to give a solid The solid was recrystallized from MeOH

实验步骤: 投料: 使用氢化铝锂固体自己配成2.5MTHF溶液(1.8 g固体加至19 mLTHF中，超声助溶，得浑浊液)： 往250 mL单口瓶中，加入底物(5 g, 1 eq.)，加入THF120 mL。冰水浴下滴加：2.5 M LiAlH4(19 mL, 2 eq.) 混合物在冰水浴下搅拌。 12-08 13:30: 反应混合物通过TLC监测（展开剂DCM:MeOH=20:1 ,rf:0.4）原料剩余大部分，有微弱产物点。 补加2.5 M LiAlH4(0.2 mL, 1 eq.)，室温下搅拌 17:30 TLC 产物点变浓 补加2.5 M LiAlH4(0.2 mL, 1 eq.) 12-9 9:00 TLC只有产物点为主点，LCMS(114615-1-3-R)主峰为产物峰

实验步骤: 投料: 使用氢化铝锂固体自己配成2.5MTHF溶液： 往20 mL单口瓶中，加入底物(106 mg, 1 eq.)，置换N2，加入THF2.5 mL。冰水浴下滴加：2.5 M LiAlH4(0.2 mL, 1 eq.) 混合物在冰水浴下搅拌。 \n监测: 反应混合物通过TLC监测（展开剂DCM:MeOH=20:1 ,rf:0.4）原料剩余大部分，有微弱产物点。 补加2.5 M LiAlH4(0.2 mL, 1 eq.)，室温下搅拌 17:30 TLC 产物点变浓 补加2.5 M LiAlH4(0.2 mL, 1 eq.) 12-9 9:00 TLC只有产物点为主点，LCMS(114615-1-3-R)主峰为产物峰

实验步骤: 投料: 分两个平行反应： 往20 mL单口瓶中，加入底物(106 mg, 1 eq.)，置换N2，加入THF2.5 mL。冰水浴下滴加： R1:2.5 M LiAlH4(0.1 mL, 0.5 eq.) R2:2.5 M LiAlH4(0.2 mL, 1 eq.) 混合物在冰水浴下搅拌。\n监测: 反应混合物通过TLC监测（展开剂DCM:MeOH=20:1 ,rf:0.4）未反应。 体系浑浊至难以搅拌，补加2 mLTHF，室温下搅拌 12-08 9:00 TLC 未反应

实验步骤: 监测: 反应混合物通过TLC监测（展开剂DCM:MeOH=20:1 ,rf:0.5）和小试相同，原料:产物约1:1。 加酒石酸钾钠水溶液淬灭，EA萃取，有机相干燥旋干，过柱(DCM:MeOH=60:1)，得橙色油状产物0.53 g，回收原料粉色固体1.51 g。\n投料: 往500 mL单口瓶中，加入底物(5.03 g, 1 eq.)，甲苯230 mL。置换N2后，冰水浴下滴加1M DIBAH(95 mL, 4 eq.)，冰水浴下反应。