1-溴-2-丙烷-2-基苯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of 1-bromo-2-isopropylbenzene (2.50 g, 12.56 mmol) in anhydrous THF (40 mL), 2,2′-dipyridyl (ca 2 mg) was added under nitrogen atmosphere (Zhi et al., 2003, which is incorporated herein by reference). The mixture was cooled down minus 78° C., and a solution of n-butyllithium (5.52 mL, 2.5 M in hexanes, 13.82 mmol) was added dropwise via syringe within the period of ten minutes. Upon addition, the mixture was stirred for 30 minutes, then warmed up to minus 30° C., and a flow of formaldehyde (generated from 1.77 g of paraformaldehyde by heating at 160° C.) was passed through the solution until the deep red color disappeared completely. The mixture was quenched with saturated ammonium chloride (5 mL), then poured into brine (15 mL). Organic layer was separated; aqueous layer was extracted twice with dichloromethane (20 mL each); combined extracts were dried over anhydrous Na2SO4, evaporated, and purified by silica gel chromatography to yield 2-isopropylbenzyl alcohol (1.11 g, 59%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 3H, Ph-H), 7.18 (m, 3H, Ph-H), 4.75 (s, 2H, CH2OH), 3.27 (sep, J=6.6 Hz, 1H, CH(CH3)2), 1.53 (s, 1H, CH2OH), 1.26 (d, J=6.6 Hz, 1H, CH(CH3)2). Upon addition warmed up to minus 30° C. The mixture was quenched with saturated ammonium chloride (5 mL) poured into brine (15 mL) Organic layer was separated aqueous layer was extracted twice with dichloromethane (20 mL each) combined extracts were dried over anhydrous Na2SO4 evaporated purified by silica gel chromatography

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 110.7 mg (0.38 mmol) 4-(3′-Benzylphenyl)-3-(S)-isopropyl-piperazine (88a), 123.5 mg (0.62 mmol, 1.65 eq.) 1-Bromo-2-isopropyl-benzene 11.7 mg (12.7 μmol, 0.034 eq.) Pd2(dba)3, 7.4 mg (19.3 μmol, 0.05 eq.) 2-Diphenylphosphino-2′-dimethylamino-biphenyl and 87.3 mg (0.91 mmol, 2.42 eq.) NaOt-Bu were dissolved in 5 ml dry toluene. The resulting mixture was heated under N2 at 80° C. for 15.5 h. After cooling to room temperature the mixture was diluted with ether and washed with brine. The comb. org. fractions were dried over Na2SO4 and evaporated. Column chromatography (hexanes/EtOAc (9+1)) yielded 96.5 mg (0.23 mmol, 62.20%) 1-(3-Benzyl-phenyl)-2-(S)-isopropyl-4-(2-isopropyl-phenyl)-piperazine (89) as a clear oil. After cooling to room temperature the mixture washed with brine fractions were dried over Na2SO4 evaporated

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

实验步骤: (CyPF-t-Bu)PdCl2 (73.0 mg, 100 mmol), LiNH2 (2.30 g, 100 mmol) and 1-Bromo-2-i-propylbenzene (1.99 g, 100 mmol) were weighed into a 100 mL round bottom flask with a stirring bar. DME (20.0 mL) was then added. The flask was sealed with a cap and wrapped tightly with electrical tape. The reaction mixture was stirred for 24 h at 90° C. The reaction mixture was allowed to cool to room temperature before pouring into ice water (50.0 mL). To this mixture was added aqueous HCl (100 mL, 1.0 M). The mixture was stirred at room temperature for 5 min and was then neutralized with a saturated solution of NaHCO3 (50.0 mL). After extraction with CH2Cl2 (3×50.0 mL), the organic layer was separated and dried over MgSO4. The solvent was evaporated, and the crude product isolated by column chromatography, eluting with hexane/ethyl acetate (70/30) to give 1.11 g (82%) of 2-i-propylaniline as a solid. The flask was sealed with a cap to cool to room temperature The mixture was stirred at room temperature for 5 min After extraction with CH2Cl2 (3×50.0 mL) the organic layer was separated dried over MgSO4 The solvent was evaporated the crude product isolated by column chromatography eluting with hexane/ethyl acetate (70/30)

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

实验步骤: Several drops of a 12 mL tetrahydrofuran solution of 8.2 g of 1-bromo-2-isopropylbenzene were added to a 5 mL tetrahydrofuran solution of 1.2 g of magnesium under a nitrogen atmosphere to initiate the reaction, after which the rest was gradually added drop-wise at a rate at which heating reflux was maintained. Upon completion of the dropping, the reaction mixture was refluxed for 0.5 hour in an oil bath, and then cooled to room temperature. A reagent prepared as above was gradually added drop-wise under ice cooling and a nitrogen atmosphere to a suspension of 3 g of 5-chloro-1H-indol-2,3-dione in 22 mL of tetrahydrofuran. Upon completion of the dropping, the temperature was raised to room temperature, and then the reaction mixture was stirred for 2 hours at that temperature. A 3N hydrochloric acid aqueous solution was poured into the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate, and the drying agent was then filtered off and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate/hexane=1/2; v/v) to obtain 4.9 g of the titled compound (pale yellow, amorphous). the reaction heating reflux was maintained Upon completion of the dropping, the reaction mixture was refluxed for 0.5 hour in an oil bath A reagent prepared Upon completion of the dropping, the temperature was raised to room temperature The organic layer was washed with water and saturated brine dried with magnesium sulfate the drying agent was then filtered off the solvent was distilled off under reduced pressure The residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate/hexane=1/2; v/v)

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

实验步骤: To a solution of 1-bromo-2-isopropylbenzene (2.50 g, 12.56 mmol) in anhydrous THF (40 mL), 2,2′-dipyridyl (ca 2 mg) was added under nitrogen atmosphere (Zhi et al., 2003, which is incorporated herein by reference). The mixture was cooled down minus 78° C., and a solution of n-butyllithium (5.52 mL, 2.5 M in hexanes, 13.82 mmol) was added dropwise via syringe within the period of ten minutes. Upon addition, the mixture was stirred for 30 minutes, then warmed up to minus 30° C., and a flow of formaldehyde (generated from 1.77 g of paraformaldehyde by heating at 160° C.) was passed through the solution until the deep red color disappeared completely. The mixture was quenched with saturated ammonium chloride (5 mL), then poured into brine (15 mL). Organic layer was separated; aqueous layer was extracted twice with dichloromethane (20 mL each); combined extracts were dried over anhydrous Na2SO4, evaporated, and purified by silica gel chromatography to yield 2-isopropylbenzyl alcohol (1.11 g, 59%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 3 H, Ph-H), 7.18 (m, 3 H, Ph-H), 4.75 (s, 2 H, CH2OH), 3.27 (sep, J=6.6 Hz, 1 H, CH(CH3)2), 1.53 (s, 1 H, CH2OH), 1.26 (d, J=6.6 Hz, 1 H, CH(CH3)2). Upon addition warmed up to minus 30° C. The mixture was quenched with saturated ammonium chloride (5 mL) poured into brine (15 mL) Organic layer was separated aqueous layer was extracted twice with dichloromethane (20 mL each) combined extracts were dried over anhydrous Na2SO4 evaporated purified by silica gel chromatography

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

实验步骤: To a solution of 1-bromo-2-isopropylbenzene (2.50 g, 12.56 mmol) in anhydrous THF (40 mL), 2,2′-dipyridyl (ca 2 mg) was added under nitrogen atmosphere (Zhi et al., 2003, which is incorporated herein by reference). The mixture was cooled down minus 78° C., and a solution of n-butyllithium (5.52 mL, 2.5 M in hexanes, 13.82 mmol) was added dropwise via syringe within the period of ten minutes. Upon addition, the mixture was stirred for 30 minutes, then warmed up to minus 30° C., and a flow of formaldehyde (generated from 1.77 g of paraformaldehyde by heating at 160° C.) was passed through the solution until the deep red color disappeared completely. The mixture was quenched with saturated ammonium chloride (5 mL), then poured into brine (15 mL). Organic layer was separated; aqueous layer was extracted twice with dichloromethane (20 mL each); combined extracts were dried over anhydrous Na2SO4, evaporated, and purified by silica gel chromatography to yield 2-isopropylbenzyl alcohol (1.11 g, 59%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 3 H, Ph-H), 7.18 (m, 3 H, Ph-H), 4.75 (s, 2 H, CH2OH), 3.27 (sep, J=6.6 Hz, 1 H, CH(CH3)2), 1.53 (s, 1 H, CH2OH), 1.26 (d, J=6.6 Hz, 1 H, CH(CH3)2). Upon addition warmed up to minus 30° C. The mixture was quenched with saturated ammonium chloride (5 mL) poured into brine (15 mL) Organic layer was separated aqueous layer was extracted twice with dichloromethane (20 mL each) combined extracts were dried over anhydrous Na2SO4 evaporated purified by silica gel chromatography

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

实验步骤: To a solution of 1-bromo-2-isopropylbenzene (2.50 g, 12.56 mmol) in anhydrous THF (40 mL), 2,2′-dipyridyl (ca 2 mg) was added under nitrogen atmosphere (Zhi et al., 2003, which is incorporated herein by reference). The mixture was cooled down minus 78° C., and a solution of n-butyllithium (5.52 mL, 2.5 M in hexanes, 13.82 mmol) was added dropwise via syringe within the period of ten minutes. Upon addition, the mixture was stirred for 30 minutes, then warmed up to minus 30° C., and a flow of formaldehyde (generated from 1.77 g of paraformaldehyde by heating at 160° C.) was passed through the solution until the deep red color disappeared completely. The mixture was quenched with saturated ammonium chloride (5 mL), then poured into brine (15 mL). Organic layer was separated; aqueous layer was extracted twice with dichloromethane (20 mL each); combined extracts were dried over anhydrous Na2SO4, evaporated, and purified by silica gel chromatography to yield 2-isopropylbenzyl alcohol (1.11 g, 59%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 3H, Ph-H), 7.18 (m, 3H, Ph-H), 4.75 (s, 2H, CH2OH), 3.27 (sep, J=6.6 Hz, 1H, CH(CH3)2), 1.53 (s, 1H, CH2OH), 1.26 (d, J=6.6 Hz, 1H, CH(CH3)2). Upon addition warmed up to minus 30° C. The mixture was quenched with saturated ammonium chloride (5 mL) poured into brine (15 mL) Organic layer was separated aqueous layer was extracted twice with dichloromethane (20 mL each) combined extracts were dried over anhydrous Na2SO4 evaporated purified by silica gel chromatography

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

实验步骤: n-Butyllithium (2.5M, 100 mL) was added with stirring under nitrogen at 0°-5° C. during ten minutes to a solution of 2-isopropylbromobenzene in anhydrous ether (500 mL). The mixture was allowed to warm to room temperature, stirred at room temperature for six hours, and cooled to -60° C. A solution of diethylcarbamyl chloride (34 g) in anhydrous ether (50 mL) was added during 20 minutes while maintaining the temperature below -50° C. The temperature was allowed to rise to room temperature during one hour. Water (100 mL) was added. The ether layer was washed with saturated aqueous sodium chloride (200 mL), dried over magnesium sulfate and stripped of ether. Distillation of the residue (80°-90° C./0.1 mm Hg) gave 2-isopropyl-N,N-diethylbenzamide (44 g, 80% yield). cooled to -60° C while maintaining the temperature below -50° C to rise to room temperature during one hour The ether layer was washed with saturated aqueous sodium chloride (200 mL) dried over magnesium sulfate Distillation of the residue (80°-90° C./0.1 mm Hg)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 110.7 mg (0.38 mmol) 4-(3′-Benzylphenyl)-3-(S)-isopropyl-piperazine (88a), 123.5 mg (0.62 mmol, 1.65 eq.) 1-Bromo-2-isopropyl-benzene 11.7 mg (12.7 μmol, 0.034 eq.) Pd2(dba)3, 7.4 mg (19.3 μmol, 0.05 eq.) 2-Diphenylphosphino-2′-dimethylamino-biphenyl and 87.3 mg (0.91 mmol, 2.42 eq.) NaOt-Bu were dissolved in 5 ml dry toluene. The resulting mixture was heated under N2 at 80° C. for 15.5 h. After cooling to room temperature the mixture was diluted with ether and washed with brine. The comb. org. fractions were dried over Na2SO4 and evaporated. Column chromatography (hexanes/EtOAc (9+1)) yielded 96.5 mg (0.23 mmol, 62.20%) 1-(3-Benzyl-phenyl)-2-(S)-isopropyl-4-(2-isopropyl-phenyl)-piperazine (89) as a clear oil. After cooling to room temperature the mixture washed with brine fractions were dried over Na2SO4 evaporated

反应条件: temp:0.00; pressure:0.00; stir: