1-乙基-1-对甲苯磺酰甲基异腈

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Iodoethane (3.99 g, 25.61 mmol) was added to a solution of 1-isocyanomethanesulfonyl-4-methyl-benzene (5 g, 25.61 mmol) in anhydrous THF (20 ml). The mixture was cooled to −78° C. and potassium tert-butoxide (31 ml of a 1 M solution in THF, 31 mmol) was added dropwise over 15 minutes. The mixture was warmed to room temperature over 1 h. Water (50 ml) was added and the solution was extracted with diethylether and dried over Na2SO4 and evaporated to dryness. The resulting brown oily material was used without purification. The resulting 1-(1-Isocyano-propane-1-sulfonyl)-4-methyl-benzene (4.29 g, 19.05 mmol) and acrylonitrile (1.26 ml, 19.05 mmol) were stirred in anhydrous THF (20 ml). The mixture was cooled to 0° C. and potassium tert-butoxide in THF (38.1 ml, 38.1 mmol) was added dropwise. The mixture was heated to reflux for 2 h then left at room temperature overnight, and then concentrated in vacuo. EtOAc (30 ml) was added to the brown solid and the mixture was stirred at room temperature for a few hours, filtered and the solid washed well with EtOAc. The EtOAc solution was concentrated in vacuo and purified by flash chromatography eluting with EtOAc/n-hexanes mixture: 3:2 to afford the title compound. (0.856 g). The mixture was warmed to room temperature over 1 h the solution was extracted with diethylether dried over Na2SO4 evaporated to dryness The resulting brown oily material was used without purification The mixture was cooled to 0° C. The mixture was heated to reflux for 2 h concentrated in vacuo EtOAc (30 ml) was added to the brown solid filtered the solid washed well with EtOAc The EtOAc solution was concentrated in vacuo purified by flash chromatography eluting with EtOAc/n-hexanes mixture

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Iodoethane (3.99 g, 25.61 mmol) was added to a solution of 1-isocyanomethanesulfonyl-4-methyl-benzene (5 g, 25.61 mmol) in anhydrous THF (20 ml). The mixture was cooled to −78° C. and potassium tert-butoxide (31 ml of a 1 M solution in THF, 31 mmol) was added dropwise over 15 minutes. The mixture was warmed to room temperature over 1 h. Water (50 ml) was added and the solution was extracted with diethylether and dried over Na2SO4 and evaporated to dryness. The resulting brown oily material was used without purification. The resulting 1-(1-Isocyano-propane-1-sulfonyl)-4-methyl-benzene (4.29 g, 19.05 mmol) and acrylonitrile (1.26 ml, 19.05 mmol) were stirred in anhydrous THF (20 ml). The mixture was cooled to 0° C. and potassium tert-butoxide in THF (38.1 ml, 38.1 mmol) was added dropwise. The mixture was heated to reflux for 2 h then left at room temperature overnight, and then concentrated in vacuo. EtOAc (30 ml) was added to the brown solid and the mixture was stirred at room temperature for a few hours, filtered and the solid washed well with EtOAc. The EtOAc solution was concentrated in vacuo and purified by flash chromatography eluting with EtOAc/n-hexanes mixture: 3:2 to afford the title compound. (0.856 g). The mixture was warmed to room temperature over 1 h the solution was extracted with diethylether dried over Na2SO4 evaporated to dryness The resulting brown oily material was used without purification The mixture was cooled to 0° C. The mixture was heated to reflux for 2 h concentrated in vacuo EtOAc (30 ml) was added to the brown solid filtered the solid washed well with EtOAc The EtOAc solution was concentrated in vacuo purified by flash chromatography eluting with EtOAc/n-hexanes mixture

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

实验步骤: A mixture of 1-(1-isocyanopropylsulfonyl)-4-methylbenzene (1.21 g, 5.40 mmol), 4-bromobenzaldehyde (1 g, 5 mmol), and K2CO3 (0.896 g, 6.49 mmol) in MeOH (27 mL) was heated at reflux overnight. The reaction was cooled to ambient temperature and the solvent was evaporated at reduced pressure. The residue was partitioned between water and EtOAc. The separated organic phase was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was dissolved in minimal toluene, loaded on silica gel, and eluted with 2 column volumes of hexane, then 10% to 50% EtOAc/hexanes. The result was 1.27 g (93%) of the title compound. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.60-7.54 (m, 2H), 7.49-7.43 (m, 2H), 2.78 (q, J=7.5, 2H), 1.32 (t, J=7.6, 3H). MS (DCI+) m/z 252/254 (M+H). was heated at reflux overnight the solvent was evaporated at reduced pressure The residue was partitioned between water and EtOAc The separated organic phase was washed with water and brine dried (Na2SO4) filtered concentrated in vacuo The crude product was dissolved in minimal toluene eluted with 2 column volumes of hexane

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

实验步骤: A mixture of 1-(1-isocyanopropylsulfonyl)-4-methylbenzene (1.55 g, 6.94 mmol), 2-fluoro-4-(trifluoromethyl)benzaldehyde (0.95 mL, 6.9 mmol), and K2CO3 (1.15 g, 8.33 mmol) in MeOH (35 mL) was heated at reflux overnight. The reaction was cooled to ambient temperature and the volatiles evaporated at reduced pressure. The residue was diluted with water and the product extracted with EtOAc. The combined organic extract was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel (Analogix® 40×150 column, 10%-70% EtOAc/hexanes) to yield 0.89 g (50%) of the title compound. 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.67-7.60 (m, 1H), 7.53-7.48 (m, 1H), 7.47-7.42 (m, 1H), 2.67 (qd, J=7.5, 1.6, 2H), 1.29 (t, J=7.5, 3H). MS (DCI+) m/z 260 (M+H). was heated at reflux overnight the volatiles evaporated at reduced pressure The residue was diluted with water the product extracted with EtOAc The combined organic extract was washed with water and brine dried (Na2SO4) filtered concentrated in vacuo The crude product was chromatographed on silica gel (Analogix® 40×150 column, 10%-70% EtOAc/hexanes)

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

实验步骤: A mixture of 1-(1-isocyanopropylsulfonyl)-4-methylbenzene (1.98 g, 8.87 mmol), 5-bromopicolinaldehyde (1.65 g, 8.87 mmol), and K2CO3 (1.47 g, 10.6 mmol) in MeOH (45 mL) was heated at reflux overnight. The reaction was cooled to ambient temperature and concentrated in vacuo. Water was added to the residue and the product was extracted with EtOAc. The combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel (Analogix® 25×60 column, 10%-50% EtOAc/hexanes) to yield 1.97 g (88%) of the title compound. 1H NMR (300 MHz, CDCl3) δ 8.68 (dd, J=2.4, 0.5, 1H), 7.89-7.82 (m, 2H), 7.55-7.49 (m, 1H), 3.06 (q, J=7.5, 2H), 1.29 (t, J=7.5, 3H). MS (DCI+) m/z 253/255 (M+H). was heated at reflux overnight concentrated in vacuo Water was added to the residue the product was extracted with EtOAc The combined organic extract was washed with brine dried (Na2SO4) filtered concentrated in vacuo The crude product was chromatographed on silica gel (Analogix® 25×60 column, 10%-50% EtOAc/hexanes)

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

实验步骤: A mixture of 4-(trifluoromethyl)benzaldehyde (3.60 mL, 27.0 mmol), 1-(1-isocyanopropylsulfonyl)-4-methylbenzene (6.02 g, 27.0 mmol), and K2CO3 (4.47 g, 32.4 mmol) in MeOH (100 mL) was heated to reflux. After 1.5 hr the reaction mixture was cooled to ambient temperature, and the volatiles evaporated at reduced pressure. The residue was partitioned between Et2O (100 mL) and H2O (100 mL). The separated aqueous phase was extracted with Et2O. The combined organic extract was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. Chromatography on silica gel (Analogix® Intelliflash 280™; SF40-150 g column; 10% to 30% EtOAc/hexanes eluant, 30 min) afforded 5.75 g (88%) of the title compound as a pale yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 8.44 (s, 1H), 7.90-7.78 (m, 4H), 2.79 (q, J=7.5, 2H), 1.23 (t, J=7.5, 3H). MS (DCI+) m/z 242 (M+H). was heated to reflux the volatiles evaporated at reduced pressure The residue was partitioned between Et2O (100 mL) and H2O (100 mL) The separated aqueous phase was extracted with Et2O The combined organic extract was washed with brine dried (MgSO4) filtered concentrated in vacuo