五甲基哌啶

反应条件: temp:25.01; pressure:0.00; stir:

反应条件: temp:25.01; pressure:0.00; stir:

反应条件: temp:25.01; pressure:0.00; stir:

反应条件: temp:25.01; pressure:0.00; stir:

反应条件: temp:25.01; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 6-bromo-4-chloro-3-nitro-quinoline (Stage A.4, 3.0 g, 20.43 mmol) and 4-amino-1,3-dimethylpyrazole.HCl (ChemCollect, Remscheid, Germany, 1.85 g, 12.53 mmol) in DMA (45 ml) was added 1,2,2,6,6-pentamethylpiperidine (6.67 ml, 36.5 mmol). The RM was stirred at 50° C. for 4.5 h. Then the RM was cooled down to rt and quenched with H2O. The suspension was filtered, the solid cake was washed with H2O and dried under vacuum, before being dissolved in EtOAc. The solution was washed with brine (2×), dried over Na2SO4, filtered and evaporated to dryness to give the title compound as an orange solid (HPLC tR 2.55 min (Method A); M+H=362; M−H=360 MS-ES) Then the RM was cooled down to rt quenched with H2O The suspension was filtered the solid cake was washed with H2O dried under vacuum before being dissolved in EtOAc The solution was washed with brine (2×) dried over Na2SO4 filtered evaporated to dryness

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 6-bromo-4-chloro-3-nitro-quinoline (Stage A.4, 3.0 g, 20.43 mmol) and 4-amino-1,3-dimethylpyrazole.HCl (ChemCollect, Remscheid, Germany, 1.85 g, 12.53 mmol) in DMA (45 ml) was added 1,2,2,6,6-pentamethylpiperidine (6.67 ml, 36.5 mmol). The RM was stirred at 50° C. for 4.5 h. Then the RM was cooled down to rt and quenched with H2O. The suspension was filtered, the solid cake was washed with H2O and dried under vacuum, before being dissolved in EtOAc. The solution was washed with brine (2×), dried over Na2SO4, filtered and evaporated to dryness to give the title compound as an orange solid (HPLC tR 2.55 min (Method A); M+H=362; M−H=360 MS-ES) Then the RM was cooled down to rt quenched with H2O The suspension was filtered the solid cake was washed with H2O dried under vacuum before being dissolved in EtOAc The solution was washed with brine (2×) dried over Na2SO4 filtered evaporated to dryness

实验步骤: 投料: 取50ml干燥双口瓶，氮气置换后加入用超干四氢呋喃（5ml）溶解的第一步M-C4X-147113-1（0.21g 0.8mmol 1eq），冰盐浴下滴加五甲基哌啶（0.14g 0.9 mmol 1.1eq）（此时溶液由无色溶液转为白色浑浊液），滴加完毕后反应液冰盐浴下搅拌20min后，升至室温搅拌3h。反应液冰盐浴下逐滴加入用超干四氢呋喃（3ml）溶解的手性醇599-04-2（0.13g 1mmol 1.2eq），滴加时间为2min，滴毕后，保温反应2h。 LCMS监测（147113-s2-wjj），无反应。

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

实验步骤: First, ethyl 1-naphthylpropiolate was prepared. A mixture of 1-ethynylnaphthalene (7.7 g, 50.6 mmol), 4-(dimethylamino)pyridine (0.06 g, 0.5 mmol), 1,2,2,6,6-pentamethylpiperidine (8.8 g, 55.7 mmol), and acetonitrile (120 mL) was sparged with nitrogen for 10 min, and then tetrakis(triphenylphosphine)palladium(0) (1.3 g, 1.1 mmol) was added. The mixture was sparged with nitrogen for 10 min, heated to reflux, treated dropwise with ethyl chloroformate (12.1 g, 111.3 mmol), and held at reflux for 2 h. The reaction mixture was cooled to ambient and diluted with ligroin. The solution was washed three times with water and then with brine, dried (Na2SO4), and concentrated to deposit a brown oil. The crude product was purified by column chromatography to provide 4.0 g (36% of theory) of ethyl 1-naphthylpropiolate. 1H NMR (CDCl3): δ 1.40 (t, 3H), 4.33 (q, 2H), 7.50 (m, 3H), 7.90 (m, 3H), 8.30 (d, 1H). First, ethyl 1-naphthylpropiolate was prepared was sparged with nitrogen for 10 min The mixture was sparged with nitrogen for 10 min heated to reflux at reflux for 2 h The reaction mixture was cooled to ambient and The solution was washed three times with water with brine, dried (Na2SO4) concentrated The crude product was purified by column chromatography

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

实验步骤: First, ethyl 1-naphthylpropiolate was prepared. A mixture of 1-ethynylnaphthalene (7.7 g, 50.6 mmol), 4-(dimethylamino)pyridine (0.06 g, 0.5 mmol), 1,2,2,6,6-pentamethylpiperidine (8.8 g, 55.7 mmol), and acetonitrile (120 mL) was sparged with nitrogen for 10 min, and then tetrakis(triphenylphosphine)palladium(0) (1.3 g, 1.1 mmol) was added. The mixture was sparged with nitrogen for 10 min, heated to reflux, treated dropwise with ethyl chloroformate (12.1 g, 111.3 mmol), and held at reflux for 2 h. The reaction mixture was cooled to ambient and diluted with ligroin. The solution was washed three times with water and then with brine, dried (Na2SO4), and concentrated to deposit a brown oil. The crude product was purified by column chromatography to provide 4.0 g (36% of theory) of ethyl 1-naphthylpropiolate. 1H NMR (CDCl3): δ 1.40 (t, 3H), 4.33 (q, 2H), 7.50 (m, 3H), 7.90 (m, 3H), 8.30 (d, 1H). First, ethyl 1-naphthylpropiolate was prepared was sparged with nitrogen for 10 min The mixture was sparged with nitrogen for 10 min heated to reflux at reflux for 2 h The reaction mixture was cooled to ambient and The solution was washed three times with water with brine, dried (Na2SO4) concentrated The crude product was purified by column chromatography

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.42 g (0.36 mmol) of tetrakis(triphenylphosphine)palladium(0), 20 mg (0.16 mmol) of 4-dimethylamino-pyridine and 2.87 g (18.5 mmol) of 1,2,2,6,6-penta-methylpiperidine are introduced into 30 ml of dichloromethane in a 60 ml autoclave under argon. Then 10 bar of acetylene are injected, and the autoclave is heated to 40° C. 5 g (36.6 mmol) of n-butyl chloroformate are pumped in over the course of 10 min, and then acetylene is further injected to 20 bar. The amount of acetylene taken up is replenished hourly over the course of 24 h, and, after cooling, the reaction discharge is flushed with nitrogen and the reaction mixture is distilled. n-Butyl propiolate is isolated in 85% yield. are pumped in over the course of 10 min taken up is replenished hourly over the course of 24 h after cooling the reaction discharge is flushed with nitrogen the reaction mixture is distilled

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

实验步骤: 0.25 g (1.1 mmol) of palladium(II) acetate and 1.16 g (4.4 mmol) of triphenylphosphine are introduced into 100 ml of dichloromethane in a 250 ml round-bottomed flask under argon. The yellow solution is stirred at room temperature for 1 h. Then 0.06 g (0.5 mmol) of 4-dimethylaminopyridine, 8.53 g (55.5 mmol) of 1,2,2,6,6-pentamethylpiperidine and 5.1 g (50 mmol) of phenylacetylene are added. The mixture is heated to reflux at 40° C. and then 6.83 g (50 mmol) of n-butyl chloroformate are added dropwise over the course of 1 h. After a reaction time of 20 h, the reaction mixture is worked up by distillation to isolate n-butyl phenylpropynoate in 85% yield. The mixture is heated to reflux at 40° C. After a reaction time of 20 h, the reaction mixture is worked up by distillation