4-chloro-2-iodo-1-methylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-chloro-2-iodo-1-methylbenzene (5.05 g, 20 mmol) in 100 mL of anhydrous THF was cooled to −100° C. (liquid nitrogen/EtOH) under nitrogen. Then 1.4M solution of sec-BuLi in cyclohexane (15 mL, 21 mmol) was added dropwise at −100° C. to −90° C. The mixture was stirred at −100° C. to −90° C. for 10 min, then a solution of R-(+)-propylene oxide (1.51 g, 1.8 mL, 26 mmol) in 15 mL of THF was added dropwise at −100° C. to −90° C., then the mixture was cooled to −105° C. and a 46.5% solution of BF3 in diethyl ether (4.18 mL, 30 mmol) was added dropwise. The mixture was stirred at −100° C. to −90° C. for 2 h, then the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C. The mixture was stirred and warmed to 0° C. overnight. Then 20 mL of water was added and mixture was extracted with EtOAc (2×60 mL), the extract was dried over Na2SO4 and evaporated to give crude oil, which was purified by column (silica gel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7) to give (2R)-1-(5-chloro-2-methylphenyl)propan-2-ol (1.39 g, 38%) as pale yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.16 (s, 1H), 7.10 (m, 2H), 4.03 (m, 1H), 2.73 (m, 2H), 2.29 (s, 3H), 1.86 (s, 1H), 1.27 (d, J=6.24 Hz, 3H). The mixture was stirred at −100° C. to −90° C. for 2 h the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C The mixture was stirred warmed to 0° C. overnight Then 20 mL of water was added mixture was extracted with EtOAc (2×60 mL) the extract was dried over Na2SO4 evaporated to give crude oil, which was purified by column (silica gel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7)

反応条件: temp:-105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-chloro-2-iodo-1-methylbenzene (5.05 g, 20 mmol) in 100 mL of anhydrous THF was cooled to −100° C. (liquid nitrogen/EtOH) under nitrogen. Then 1.4M solution of sec-BuLi in cyclohexane (15 mL, 21 mmol) was added dropwise at −100° C. to −90° C. The mixture was stirred at −100° C. to −90° C. for 10 min, then a solution of R-(+)-propylene oxide (1.51 g, 1.8 mL, 26 mmol) in 15 mL of THF was added dropwise at −100° C. to −90° C., then the mixture was cooled to −105° C. and a 46.5% solution of BF3 in diethyl ether (4.18 mL, 30 mmol) was added dropwise. The mixture was stirred at −100° C. to −90° C. for 2 h, then the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C. The mixture was stirred and warmed to 0° C. overnight. Then 20 mL of water was added and mixture was extracted with EtOAc (2×60 mL), the extract was dried over Na2SO4 and evaporated to give crude oil, which was purified by column (silica gel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7) to give (2R)-1-(5-chloro-2-methylphenyl)propan-2-ol (1.39 g, 38%) as pale yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.16 (s, 1H), 7.10 (m, 2H), 4.03 (m, 1H), 2.73 (m, 2H), 2.29 (s, 3H), 1.86 (s, 1H), 1.27 (d, J=6.24 Hz, 3H). The mixture was stirred at −100° C. to −90° C. for 2 h the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C The mixture was stirred warmed to 0° C. overnight Then 20 mL of water was added mixture was extracted with EtOAc (2×60 mL) the extract was dried over Na2SO4 evaporated to give crude oil, which was purified by column (silica gel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-chloro-2-iodo-1-methylbenzene (3.95 g, 15.6 mmol), N-bromosuccinimide (3.10 g, 17.6 mmol), and benzoyl peroxide (0.1 g) in carbon tetrachloride (100 mL) was heated to reflux for 48 hours, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes to provide 3.34 g (64%) of the desired product. MS (DCI/NH3) m/z 330, 332 (M+H)+; 1H NMR (CDCl3) δ 7.85 (d, 1H), 7.40-7.32 (m, 2H), 4.59 (s, 2H). was heated to reflux for 48 hours filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-chloro-2-iodo-1-methylbenzene (3.95 g, 15.6 mmol), N-bromosuccinimide (3.10 g, 17.6 mmol), and benzoyl peroxide (0.1 g) in carbon tetrachloride (100 mL) was heated to reflux for 48 hours, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes to provide 3.34 g (64%) of the desired product. MS (DCI/NH3) m/z 330, 332 (M+H)+; 1H NMR (CDCl3) δ 7.85 (d, 1H), 7.40-7.32 (m, 2H), 4.59 (s, 2H). was heated to reflux for 48 hours filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes

反応条件: temp:-105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-chloro-2-iodo-1-methylbenzene (5.05 g, 20 mmol) in 100 mL of anhydrous THF was cooled to −100° C. (liquid nitrogen/EtOH) under nitrogen. Then 1.4M solution of sec-BuLi in cyclohexane (15 mL, 21 mmol) was added dropwise at −100° C. to −90° C. The mixture was stirred at −100° C. to −90° C. for 10 min, then a solution of R-(+)-propylene oxide (1.51 g, 1.8 mL, 26 mmol) in 15 mL of THF was added dropwise at −100° C. to −90° C., then the mixture was cooled to −105° C. and a 46.5% solution of BF3 in diethyl ether (4.18 mL, 30 mmol) was added dropwise. The mixture was stirred at −100° C. to −90° C. for 2 h, then the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C. The mixture was stirred and warmed to 0° C. overnight. Then 20 mL of water was added and mixture was extracted with EtOAc (2×60 mL), the extract was dried over Na2SO4 and evaporated to give crude oil, which was purified by column (silicagel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7) to give (2R)-1-(5-chloro-2-methylphenyl)propan-2-ol (1.39 g, 38%) as pale yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.16 (s, 1H), 7.10 (m, 2H), 4.03 (m, 1H), 2.73 (m, 2H), 2.29 (s, 3H), 1.86 (s, 1H), 1.27 (d, J=6.24 Hz, 3H). The mixture was stirred at −100° C. to −90° C. for 2 h the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C The mixture was stirred warmed to 0° C. overnight Then 20 mL of water was added mixture was extracted with EtOAc (2×60 mL) the extract was dried over Na2SO4 evaporated to give crude oil, which was purified by column (silicagel, EtOAc/hexane 1:9, Rf=0.43 in EtOAc/hexane 3:7)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, to a mixture of magnesium (1.46 g, 60.0 mmol) and tetrahydrofuran (100 ml) was added a small crystal of iodine followed by 4-chloro-2-iodo-toluene (12.62 g, 50 mmol). The mixture was heated under gentle reflux in an argon atmosphere for 6 hours and then cooled to −78° C. A solution of cyanuric chloride (7.84 g, 42.5 mmol) in tetrahydrofuran (45 ml) was added over 25 minutes. After stirring at −78° C. for 1 hour, the mixture was slowly warmed to room temperature and stirred for 16 hours. The reaction mixture, cooled in an ice bath, was quenched by slow addition of hydrochloric acid (1 M, 15 ml). The mixture was diluted with water (150 ml) and extracted with dichloromethane (3×125 ml). The combined extracts was washed with water (150 ml), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (7:93) to provide 2,4-dichloro-6-(5-chloro-2-methyl-phenyl)-[1,3,5]triazine (10.2 g, 87% yield) as a white powder. The mixture was heated under gentle reflux in an argon atmosphere for 6 hours the mixture was slowly warmed to room temperature stirred for 16 hours The reaction mixture, cooled in an ice bath was quenched by slow addition of hydrochloric acid (1 M, 15 ml) The mixture was diluted with water (150 ml) extracted with dichloromethane (3×125 ml) The combined extracts was washed with water (150 ml) dried over sodium sulfate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (7:93)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, to a mixture of magnesium (1.46 g, 60.0 mmol) and tetrahydrofuran (100 ml) was added a small crystal of iodine followed by 4-chloro-2-iodo-toluene (12.62 g, 50 mmol). The mixture was heated under gentle reflux in an argon atmosphere for 6 hours and then cooled to −78° C. A solution of cyanuric chloride (7.84 g, 42.5 mmol) in tetrahydrofuran (45 ml) was added over 25 minutes. After stirring at −78° C. for 1 hour, the mixture was slowly warmed to room temperature and stirred for 16 hours. The reaction mixture, cooled in an ice bath, was quenched by slow addition of hydrochloric acid (1 M, 15 ml). The mixture was diluted with water (150 ml) and extracted with dichloromethane (3×125 ml). The combined extracts was washed with water (150 ml), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (7:93) to provide 2,4-dichloro-6-(5-chloro-2-methyl-phenyl)-[1,3,5]triazine (10.2 g, 87% yield) as a white powder. The mixture was heated under gentle reflux in an argon atmosphere for 6 hours the mixture was slowly warmed to room temperature stirred for 16 hours The reaction mixture, cooled in an ice bath was quenched by slow addition of hydrochloric acid (1 M, 15 ml) The mixture was diluted with water (150 ml) extracted with dichloromethane (3×125 ml) The combined extracts was washed with water (150 ml) dried over sodium sulfate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (7:93)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-chloro-2-iodo-1-methylbenzene (3.95 g, 15.6 mmol), N-bromosuccinimide (3.10 g, 17.6 mmol), and benzoyl peroxide (0.1 g) in carbon tetrachloride (100 mL) was heated to reflux for 48 hours, filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes to provide 3.34 g (64%) of the desired product. MS (DCI/NH3) m/z 330, 332 (M+H)30; 1H NMR (CDCl3) δ 7.85 (d, 1H), 7.40-7.32 (m, 2H), 4.59 (s, 2H). was heated to reflux for 48 hours filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 4:100 ethyl acetate/hexanes