4-(2-溴乙基)苯甲醛

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of (2-bromoethyl)benzene (100 mmol, 18.5 g) in methylene chloride (185 ml) at 0° C. was added dropwise titanium tetrachloride (200 mmol, 22 ml). The mixture was stirred for 10 minutes and alpha,alpha-dichloromethyl methyl ether (100 mmol, 9 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour and poured into saturated NaHCO3 (1 liter). Ethyl acetate (750 ml) was added and the solution was filtered through diatomaceous earth, the organic layer separated, dried (Na2SO4) and solvent removed in vacuo. The residue was triturated with hexane to afford 8.7 g of title product; m.p. 49°-52° C. The reaction mixture was stirred at room temperature for 1 hour the solution was filtered through diatomaceous earth the organic layer separated dried (Na2SO4) and solvent removed in vacuo The residue was triturated with hexane

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

实验步骤: To a solution of magnesium (4.4 g) in tetrahydrofuran (20 ml) was added dibromoethane (1.6 ml) under a nitrogen atmosphere, and the mixture was stirred for 10 minutes. To the reaction mixture was added a solution of 1-bromo-4-phenylbutane (38.8 g) in tetrahydrofuran (30 ml) over 30 minutes, and the mixture was stirred for 40 minutes. The obtained Grignard reagent was dropwise added to a solution of 4-(2-bromoethyl)benzaldehyde (32.3 g) in tetrahydrofuran (250 ml) under ice-cooling over 30 minutes and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added a saturated aqueous ammonium chloride solution (200 ml) under ice-cooling, and the mixture was extracted with ethyl acetate (200 ml). The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled away under reduced pressure to give a brown oily substance (70.5 g). The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=10:1) to give 1-[4-(2-bromoethyl)phenyl]-5-phenylpentan-1-ol (32 g) as a yellow oily substance. the mixture was stirred for 40 minutes cooling over 30 minutes the mixture was stirred at room temperature for 2 hours cooling the mixture was extracted with ethyl acetate (200 ml) The ethyl acetate layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure to give a brown oily substance (70.5 g) The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=10:1)

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

实验步骤: To a solution of dichloromethyl methyl ether (62 ml) in methylene chloride (40 ml) was added titanium tetrachloride (75 ml) over 10 minutes under a nitrogen atmosphere at 4-5° C. Then, a solution of phenethyl bromide (85 ml) in methylene chloride (50 ml) was added thereto over 50 minutes at 5-7° C. and the mixture was stirred for 5 hours while gradually raising the temperature of the mixture to room temperature. Water (200 ml) was added to the reaction mixture over 1 hour and the mixture was extracted with chloroform (200 ml). The chloroform layer was washed with water, a saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate and the solvent was distilled away under reduced pressure to give a brown oily substance (167 g). The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=20:1) to give 4-(2-bromoethyl)benzaldehyde (32.3 g) as a yellow solid, melting point 50-52° C. the mixture was extracted with chloroform (200 ml) The chloroform layer was washed with water a saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate the solvent was distilled away under reduced pressure to give a brown oily substance (167 g) The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=20:1)

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of (2-bromoethyl)benzene (100 mmol, 18.5 g) in methylene chloride (185 ml) at 0° C. was added dropwise titanium tetrachloride (200 mmol, 22 ml). The mixture was stirred for 10 minutes and alpha,alpha-dichloromethyl methyl ether (100 mmol, 9 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour and poured into saturated NaHCO3 (1 liter). Ethyl acetate (750 ml) was added and the solution was filtered through diatomaceous earth, the organic layer separated, dried (Na2SO4) and solvent removed in vacuo. The residue was triturated with hexane to afford 8.7 g of title product; m.p. 49°-52° C. The reaction mixture was stirred at room temperature for 1 hour the solution was filtered through diatomaceous earth the organic layer separated dried (Na2SO4) and solvent removed in vacuo The residue was triturated with hexane

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

实验步骤: To a mixture of 4-(bromoethyl)benzaldehyde (0.840 g, 4.2 mmol) and K2CO3 (1.75 g, 12.6 mmol) in DMF (15 mL) was added N-isopropyl-N-(piperidin-4-yl)acetamide (0.92 g, 4.2 mmol) and the reaction was stirred at room temperature 5 hours, then concentrated in vacuo. The resulting mixture was diluted with H2O and extracted with EtOAc. The organics were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 1% to 10% MeOH/CH2Cl2, afforded N-(1-(4-formylbenzyl)piperidin-4-yl)-N-isopropylacetamide (0.770 g, 61%). concentrated in vacuo The resulting mixture was diluted with H2O extracted with EtOAc The organics were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo Purification by flash chromatography on silica gel eluting with 1% to 10% MeOH/CH2Cl2

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

实验步骤: To a mixture of 4-(bromoethyl)benzaldehyde (0.840 g, 4.2 mmol) and K2CO3 (1.75 g, 12.6 mmol) in DMF (15 mL) was added N-isopropyl-N-(piperidin-4-yl)acetamide (0.92 g, 4.2 mmol) and the reaction was stirred at room temperature 5 hours, then concentrated in vacuo. The resulting mixture was diluted with H2O and extracted with EtOAc. The organics were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 1% to 10% MeOH/CH2Cl2, afforded N-(1-(4-formylbenzyl)piperidin-4-yl)-N-isopropylacetamide (0.770 g, 61%). concentrated in vacuo The resulting mixture was diluted with H2O extracted with EtOAc The organics were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo Purification by flash chromatography on silica gel eluting with 1% to 10% MeOH/CH2Cl2

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

实验步骤: To a mixture of 4-(bromoethyl)benzaldehyde (0.200 g, 1.0 mmol) and K2CO3 (0.277 g, 2.0 mmol) in DMF (5 mL) was added N-isopropylpiperazine (0.129 g, 1.0 mmol) and the reaction was stirred at room temperature for 5 hours, then concentrated in vacuo. The resulting mixture was diluted with H2O and extracted with EtOAc. The organics were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford 4-((4-Isopropylpiperazin-1-yl)methyl)benzaldehyde (0.240 g, 97%). concentrated in vacuo The resulting mixture was diluted with H2O extracted with EtOAc The organics were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

实验步骤: To a mixture of 4-(bromoethyl)benzaldehyde (0.200 g, 1.0 mmol) and K2CO3 (0.277 g, 2.0 mmol) in DMF (5 mL) was added N-isopropylpiperazine (0.129 g, 1.0 mmol) and the reaction was stirred at room temperature for 5 hours, then concentrated in vacuo. The resulting mixture was diluted with H2O and extracted with EtOAc. The organics were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford 4-((4-Isopropylpiperazin-1-yl)methyl)benzaldehyde (0.240 g, 97%). concentrated in vacuo The resulting mixture was diluted with H2O extracted with EtOAc The organics were washed with brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

实验步骤: To a solution of (2-bromoethyl)benzene (100 mmol, 18.5 g) in methylene chloride (185 ml) at 0° C. was added dropwise titanium tetrachloride (200 mmol, 22 ml). The mixture was stirred for 10 minutes and alpha,alpha-dichloromethyl methyl ether (100 mmol, 9 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour and poured into saturated NaHCO3 (1 liter). Ethyl acetate (750 ml) was added and the solution was filtered through diatomaceous earth, the organic layer separated, dried (Na2SO4) and solvent removed in vacuo. The residue was triturated with hexane to afford 8.7 g of title product; m.p. 49°-52° C. The reaction mixture was stirred at room temperature for 1 hour the solution was filtered through diatomaceous earth the organic layer separated dried (Na2SO4) and solvent removed in vacuo The residue was triturated with hexane

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

实验步骤: To a solution of magnesium (4.4 g) in tetrahydrofuran (20 ml) was added dibromoethane (1.6 ml) under a nitrogen atmosphere, and the mixture was stirred for 10 minutes. To the reaction mixture was added a solution of 1-bromo-4-phenylbutane (38.8 g) in tetrahydrofuran (30 ml) over 30 minutes, and the mixture was stirred for 40 minutes. The obtained Grignard reagent was dropwise added to a solution of 4-(2-bromoethyl)benzaldehyde (32.3 g) in tetrahydrofuran (250 ml) under ice-cooling over 30 minutes and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added a saturated aqueous ammonium chloride solution (200 ml) under ice-cooling, and the mixture was extracted with ethyl acetate (200 ml). The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled away under reduced pressure to give a brown oily substance (70.5 g). The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=10:1) to give 1-[4-(2-bromoethyl)phenyl]-5-phenylpentan-1-ol (32 g) as a yellow oily substance. the mixture was stirred for 40 minutes cooling over 30 minutes the mixture was stirred at room temperature for 2 hours cooling the mixture was extracted with ethyl acetate (200 ml) The ethyl acetate layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure to give a brown oily substance (70.5 g) The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane: ethyl acetate=10:1)