4-溴-3-氯苯腈

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-nitro-4-[2-(trimethylsilyl)ethynyl]benzonitrile (61 b) was prepared from aryl bromide 60b as an off-white solid (1.61 g, 66%): mp 81-82° C. (toluene/hexane); 1H NMR δ 8.69 (d, J=1.6 Hz, 1H), 8.20 (dd, J=8.0 and 1.6 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 8.39 min (100 area % at 254 nm). Anal. (C12H12N2O2Si) C, H, N. 3-chloro-4[(2-(trimethylsilyl)ethynyl]benzonitrile (61c). A mixture of aryl bromide 60c, (3.96 g, 18.2 mmol), (trimethylsilyl)acetylene (1.80 g, 18.23 mmol), PPh3 (0.24 g, 0.91 mol), Pd (PPh3)4 (0.11 g, 0.09 mmol), and CuI (0.17 g, 0.91 mmol) in piperidine was stirred at 90° C. for 1 h. The reaction mixture was poured into water and extracted into EtOAc. Column chromatography [hexanes/EtOAc (40:1)] gave a white solid (3.24 g, 37%); mp 82-83° C.; 1H NMR δ 8.27 (d, J=1.9 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.78 (dd, J=8.3 and 1.9 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.41 min (100 area % at 265 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-chloro-3-[2-(trimethylsilyl)ethynyl]benzonitrile (61e) was prepared from aryl iodide 60f to give a white solid (3.11 g, 88%): mp 72-73° C. (hexanes); 1H NMR δ 8.12 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.2 and 1.6 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.35 min (100 area % at 254 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-methoxy-3-[(trimethylsilyl)ethynyl]benzonitrile (61f) was prepared from aryl bromide 60g to give a white solid (8.67 g, 80%): mp 63-64° C. (hexanes; 1H NMR δ 7.87 (d, J=2.2 Hz, 1H), 7.86 (dd, J=9.7 and 2.2 Hz, 1H), 7.24 (d, J=9.7 Hz, 1H), 3.91 (s, 3H), 0.27 (s, 9H); HPLC (Method B) tR 8.31 min (98.12 area % at 254 nm). Anal. (C13H15NOSi) C, H, N. 3-Chloro-4-(3-hydroxy-3-methylbut-1-ynyl)benzonitrile (62b). 2-Methyl-3-butyn-2-ol (2.5 equiv) was added to a mixture of an aryl bromide 60c, K2CO3 (2.5 equiv), CuI (4 mol %), PPh3 (8 mol %), and 10% Pd/C (2 mol %) in DME and water. See Bleicher, L. S. et al., J. Org. Chem., 63, 1109-1118 (1998). The biphasic mixture was stirred at reflux under Ar overnight, and was then filtered (Celite) and partitioned between water and EtOAc. Column chromatography gave a white solid (4.25 g, 77%): mp 63-65° C. (hexane); 1H NMR δ 8.18 (d, J=1.5 Hz, 1H), 7.83 (dd, J=8.1 and 1.6 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.68 (s, 1H), 1.50 (s, 6H); HPLC (Method B) tR 5.00 min (100 area % at 265 nm). Anal. (C12H10ClNO) C, H, N, Cl. extracted into EtOAc

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-nitro-4-[2-(trimethylsilyl)ethynyl]benzonitrile (61 b) was prepared from aryl bromide 60b as an off-white solid (1.61 g, 66%): mp 81-82° C. (toluene/hexane); 1H NMR δ 8.69 (d, J=1.6 Hz, 1H), 8.20 (dd, J=8.0 and 1.6 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 8.39 min (100 area % at 254 nm). Anal. (C12H12N2O2Si) C, H, N. 3-chloro-4[(2-(trimethylsilyl)ethynyl]benzonitrile (61c). A mixture of aryl bromide 60c, (3.96 g, 18.2 mmol), (trimethylsilyl)acetylene (1.80 g, 18.23 mmol), PPh3 (0.24 g, 0.91 mol), Pd (PPh3)4 (0.11 g, 0.09 mmol), and CuI (0.17 g, 0.91 mmol) in piperidine was stirred at 90° C. for 1 h. The reaction mixture was poured into water and extracted into EtOAc. Column chromatography [hexanes/EtOAc (40:1)] gave a white solid (3.24 g, 37%); mp 82-83° C.; 1H NMR δ 8.27 (d, J=1.9 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.78 (dd, J=8.3 and 1.9 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.41 min (100 area % at 265 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-chloro-3-[2-(trimethylsilyl)ethynyl]benzonitrile (61e) was prepared from aryl iodide 60f to give a white solid (3.11 g, 88%): mp 72-73° C. (hexanes); 1H NMR δ 8.12 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.2 and 1.6 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.35 min (100 area % at 254 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-methoxy-3-[(trimethylsilyl)ethynyl]benzonitrile (61f) was prepared from aryl bromide 60g to give a white solid (8.67 g, 80%): mp 63-64° C. (hexanes; 1H NMR δ 7.87 (d, J=2.2 Hz, 1H), 7.86 (dd, J=9.7 and 2.2 Hz, 1H), 7.24 (d, J=9.7 Hz, 1H), 3.91 (s, 3H), 0.27 (s, 9H); HPLC (Method B) tR 8.31 min (98.12 area % at 254 nm). Anal. (C13H15NOSi) C, H, N. 3-Chloro-4-(3-hydroxy-3-methylbut-1-ynyl)benzonitrile (62b). 2-Methyl-3-butyn-2-ol (2.5 equiv) was added to a mixture of an aryl bromide 60c, K2CO3 (2.5 equiv), CuI (4 mol %), PPh3 (8 mol %), and 10% Pd/C (2 mol %) in DME and water. See Bleicher, L. S. et al., J. Org. Chem., 63, 1109-1118 (1998). The biphasic mixture was stirred at reflux under Ar overnight, and was then filtered (Celite) and partitioned between water and EtOAc. Column chromatography gave a white solid (4.25 g, 77%): mp 63-65° C. (hexane); 1H NMR δ 8.18 (d, J=1.5 Hz, 1H), 7.83 (dd, J=8.1 and 1.6 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.68 (s, 1H), 1.50 (s, 6H); HPLC (Method B) tR 5.00 min (100 area % at 265 nm). Anal. (C12H10ClNO) C, H, N, Cl. extracted into EtOAc

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc

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

实验步骤: 7.6 g (0.191 mol) of 60% strength sodium hydride in paraffin oil were initially charged in 300 ml of dioxane. At from 55° C. to 60° C., 22.9 g (0.173 mol) of diethyl malonate were added dropwise, and the mixture was stirred at 50° C. for 1-2 hours. 9.9-g (0.069 mol) of copper(1) bromide were added. At 80° C., 15 g (0.069 mol) of 3-chloro-4-bromobenzonitrile were then added dropwise, and the mixture was subsequently stirred at 100° C. for 14 hours. The reaction mixture was then cooled and acidified by dropwise addition of concentrated hydrochloric acid at from 15° C. to 20° C. Water was added, the mixture was extracted with dichloromethane, the organic phase was dried over sodium sulphate and the solvent was removed. The residue was distilled at 1 mbar, giving 17.5 g of dimethyl(2-chloro-4-cyanophenyl)malonate. the mixture was subsequently stirred at 100° C. for 14 hours The reaction mixture was then cooled the mixture was extracted with dichloromethane the organic phase was dried over sodium sulphate the solvent was removed The residue was distilled at 1 mbar

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-nitro-4-[2-(trimethylsilyl)ethynyl]benzonitrile (61 b) was prepared from aryl bromide 60b as an off-white solid (1.61 g, 66%): mp 81-82° C. (toluene/hexane); 1H NMR δ 8.69 (d, J=1.6 Hz, 1H), 8.20 (dd, J=8.0 and 1.6 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 8.39 min (100 area % at 254 nm). Anal. (C12H12N2O2Si) C, H, N. 3-chloro-4[(2-(trimethylsilyl)ethynyl]benzonitrile (61c). A mixture of aryl bromide 60c, (3.96 g, 18.2 mmol), (trimethylsilyl)acetylene (1.80 g, 18.23 mmol), PPh3 (0.24 g, 0.91 mol), Pd (PPh3)4 (0.11 g, 0.09 mmol), and CuI (0.17 g, 0.91 mmol) in piperidine was stirred at 90° C. for 1 h. The reaction mixture was poured into water and extracted into EtOAc. Column chromatography [hexanes/EtOAc (40:1)] gave a white solid (3.24 g, 37%); mp 82-83° C.; 1H NMR δ 8.27 (d, J=1.9 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.78 (dd, J=8.3 and 1.9 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.41 min (100 area % at 265 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-chloro-3-[2-(trimethylsilyl)ethynyl]benzonitrile (61e) was prepared from aryl iodide 60f to give a white solid (3.11 g, 88%): mp 72-73° C. (hexanes); 1H NMR δ 8.12 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.2 and 1.6 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.35 min (100 area % at 254 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-methoxy-3-[(trimethylsilyl)ethynyl]benzonitrile (61f) was prepared from aryl bromide 60g to give a white solid (8.67 g, 80%): mp 63-64° C. (hexanes; 1H NMR δ 7.87 (d, J=2.2 Hz, 1H), 7.86 (dd, J=9.7 and 2.2 Hz, 1H), 7.24 (d, J=9.7 Hz, 1H), 3.91 (s, 3H), 0.27 (s, 9H); HPLC (Method B) tR 8.31 min (98.12 area % at 254 nm). Anal. (C13H15NOSi) C, H, N. 3-Chloro-4-(3-hydroxy-3-methylbut-1-ynyl)benzonitrile (62b). 2-Methyl-3-butyn-2-ol (2.5 equiv) was added to a mixture of an aryl bromide 60c, K2CO3 (2.5 equiv), CuI (4 mol %), PPh3 (8 mol %), and 10% Pd/C (2 mol %) in DME and water. See Bleicher, L. S. et al., J. Org. Chem., 63, 1109-1118 (1998). The biphasic mixture was stirred at reflux under Ar overnight, and was then filtered (Celite) and partitioned between water and EtOAc. Column chromatography gave a white solid (4.25 g, 77%): mp 63-65° C. (hexane); 1H NMR δ 8.18 (d, J=1.5 Hz, 1H), 7.83 (dd, J=8.1 and 1.6 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.68 (s, 1H), 1.50 (s, 6H); HPLC (Method B) tR 5.00 min (100 area % at 265 nm). Anal. (C12H10ClNO) C, H, N, Cl. extracted into EtOAc

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Combined 4-bromo-3-chlorobenzonitrile (0.600 g, 2.77 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.32 mL, 4.16 mmol) in THF (5.54 mL), then Pd(dba)2 (0.080 g, 0.139 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.109 g, 0.277 mmol) were added and the reaction was refluxed overnight at 65° C. The reaction was concentrated by rotary evaporation and purified on a silica gel column eluting with hexanes and EtOAc to give the title compound (274 mg, 39%) as a yellow oil. MS m/z [M+H]+ 252. The reaction was concentrated by rotary evaporation purified on a silica gel column eluting with hexanes and EtOAc