5-溴-1,3-二乙基-2-碘苯

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2,6-diethyl-1-iodobenzene (10 g, 0.029 mol) in tetrahydrofuran (100 ml) at −75° C. is added n-butyl lithium (1.6 M in hexanes, 22.2 ml, 0.035 mol) dropwise maintaining the temperature of the reaction mixture below −70° C. When the addition is complete the mixture is stirred at −75° C. for an additional 30 minutes and then trimethyl borate (17.98 g, 0.17 mol) is added dropwise. After the addition is complete the reaction is stirred at −75° C. for 1 hour, then allowed to come to room temperature and stirred for 2 hours, followed by cooling in an ice bath and acidification with 0.5 N aqueous hydrochloric acid. The mixture is extracted with ethyl acetate (3×300 ml) and the organic fractions are combined, washed with brine, dried over anhydrous sodium sulphate. The mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethylphenylboronic acid (5 g) as a white solid. dropwise maintaining the temperature of the reaction mixture below −70° C When the addition After the addition is stirred at −75° C. for 1 hour to come to room temperature stirred for 2 hours by cooling in an ice bath The mixture is extracted with ethyl acetate (3×300 ml) washed with brine dried over anhydrous sodium sulphate The mixture is filtered the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica gel

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 4-bromo-2,6-diethylaniline (13.6 g, 0.06 mol) in distilled water (14 ml) is added concentrated sulphuric acid (14 ml), followed by brief heating to 60° C. for 1 hour until dissolution is complete. The mixture is allowed to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (4.1 g, 0.059 mol) in distilled water (20 ml) dropwise over 15 minutes, maintaining the temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is allowed to come to room temperature and then a solution of aqueous potassium iodide (29.8 g, 0.18 mol) in distilled water (30 ml) is added dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (150 ml×3) and the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml). The organic phase is dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethyl-1-iodobenzene (19 g) as an orange liquid. to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath maintaining the temperature below 5° C. to come to room temperature After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (150 ml×3) the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml) The organic phase is dried over anhydrous sodium sulphate concentrated under reduced pressure The residue is purified by column chromatography on silica gel

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

实验步骤: Using a procedure analogous to that used to prepare 30A, 37A (1.9 g, 5.6 mmol) was reacted with trimethyl(vinyl)silane to yield 37B (1.2 g, 90%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.14 (t, J=7.47 Hz, 6 H) 2.60 (q, J=7.62 Hz, 4 H) 5.21 (dd, J=17.80, 1.98 Hz, 1 H) 5.51 (dd, J=11.42, 1.76 Hz, 1 H) 6.64(dd, J=18.02, 11.42 Hz, 1 H) 7.18 (s, 2 H).

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

实验步骤: Using a procedure analogous to that used to prepare 30A, 37A (1.9 g, 5.6 mmol) was reacted with trimethyl(vinyl)silane to yield 37B (1.2 g, 90%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.14 (t, J=7.47 Hz, 6 H) 2.60 (q, J=7.62 Hz, 4 H) 5.21 (dd, J=17.80, 1.98 Hz, 1 H) 5.51 (dd, J=11.42, 1.76 Hz, 1 H) 6.64(dd, J=18.02, 11.42 Hz, 1 H) 7.18 (s, 2 H).

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

实验步骤: A solution of 4-bromo-2,6-diethylaniline (10 g, 44 mmol) in acetonitrile (20 mL) was added dropwise to a solution of I2 (33.4 g, 131.6 mmol), tert-butylnitrite (7.4 mL, 65.8 mmol) in acetonitrile (80 mL), never allowing the internal temperature to exceed 30° C. After stirring 4 h at ambient temperature, Na2SO3 (100 mL, saturated aqueous) was added and stirred for 1 h. The mixture was extracted with hexanes (3×200 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated. The crude oil was purified by flash chromatography (100% hexanes) to afford 37A (1.9 g, 13%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.20 (t, J=7.45 Hz, 6 H) 2.77 (q, J=7.58 Hz, 4 H) 7.18 (s, 2 H). to exceed 30° C stirred for 1 h The mixture was extracted with hexanes (3×200 mL) washed with brine dried over Na2SO4 concentrated The crude oil was purified by flash chromatography (100% hexanes)

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2,6-diethyl-1-iodobenzene (10 g, 0.029 mol) in tetrahydrofuran (100 ml) at −75° C. is added n-butyl lithium (1.6 M in hexanes, 22.2 ml, 0.035 mol) dropwise maintaining the temperature of the reaction mixture below −70° C. When the addition is complete the mixture is stirred at −75° C. for an additional 30 minutes and then trimethyl borate (17.98 g, 0.17 mol) is added dropwise. After the addition is complete the reaction is stirred at −75° C. for 1 hour, then allowed to come to room temperature and stirred for 2 hours, followed by cooling in an ice bath and acidification with 0.5 N aqueous hydrochloric acid. The mixture is extracted with ethyl acetate (3×300 ml) and the organic fractions are combined, washed with brine, dried over anhydrous sodium sulphate. The mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethylphenylboronic acid (5 g) as a white solid. dropwise maintaining the temperature of the reaction mixture below −70° C When the addition After the addition is stirred at −75° C. for 1 hour to come to room temperature stirred for 2 hours by cooling in an ice bath The mixture is extracted with ethyl acetate (3×300 ml) washed with brine dried over anhydrous sodium sulphate The mixture is filtered the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica gel

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2,6-diethyl-1-iodobenzene (10 g, 0.029 mol) in tetrahydrofuran (100 ml) at −75° C. is added n-butyl lithium (1.6 M in hexanes, 22.2 ml, 0.035 mol) dropwise maintaining the temperature of the reaction mixture below −70° C. When the addition is complete the mixture is stirred at −75° C. for an additional 30 minutes and then trimethyl borate (17.98 g, 0.17 mol) is added dropwise. After the addition is complete the reaction is stirred at −75° C. for 1 hour, then allowed to come to room temperature and stirred for 2 hours, followed by cooling in an ice bath and acidification with 0.5 N aqueous hydrochloric acid. The mixture is extracted with ethyl acetate (3×300 ml) and the organic fractions are combined, washed with brine, dried over anhydrous sodium sulphate. The mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethylphenylboronic acid (5 g) as a white solid. dropwise maintaining the temperature of the reaction mixture below −70° C When the addition After the addition is stirred at −75° C. for 1 hour to come to room temperature stirred for 2 hours by cooling in an ice bath The mixture is extracted with ethyl acetate (3×300 ml) washed with brine dried over anhydrous sodium sulphate The mixture is filtered the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica gel

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 4-bromo-2,6-diethylaniline (13.6 g, 0.06 mol) in distilled water (14 ml) is added concentrated sulphuric acid (14 ml), followed by brief heating to 60° C. for 1 hour until dissolution is complete. The mixture is allowed to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (4.1 g, 0.059 mol) in distilled water (20 ml) dropwise over 15 minutes, maintaining the temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is allowed to come to room temperature and then a solution of aqueous potassium iodide (29.8 g, 0.18 mol) in distilled water (30 ml) is added dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (150 ml×3) and the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml). The organic phase is dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethyl-1-iodobenzene (19 g) as an orange liquid. to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath maintaining the temperature below 5° C. to come to room temperature After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (150 ml×3) the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml) The organic phase is dried over anhydrous sodium sulphate concentrated under reduced pressure The residue is purified by column chromatography on silica gel

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

实验步骤: Using a procedure analogous to that used to prepare 30A, 37A (1.9 g, 5.6 mmol) was reacted with trimethyl(vinyl)silane to yield 37B (1.2 g, 90%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.14 (t, J=7.47 Hz, 6 H) 2.60 (q, J=7.62 Hz, 4 H) 5.21 (dd, J=17.80, 1.98 Hz, 1 H) 5.51 (dd, J=11.42, 1.76 Hz, 1 H) 6.64(dd, J=18.02, 11.42 Hz, 1 H) 7.18 (s, 2 H).

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

实验步骤: A solution of 4-bromo-2,6-diethylaniline (10 g, 44 mmol) in acetonitrile (20 mL) was added dropwise to a solution of I2 (33.4 g, 131.6 mmol), tert-butylnitrite (7.4 mL, 65.8 mmol) in acetonitrile (80 mL), never allowing the internal temperature to exceed 30° C. After stirring 4 h at ambient temperature, Na2SO3 (100 mL, saturated aqueous) was added and stirred for 1 h. The mixture was extracted with hexanes (3×200 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated. The crude oil was purified by flash chromatography (100% hexanes) to afford 37A (1.9 g, 13%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.20 (t, J=7.45 Hz, 6 H) 2.77 (q, J=7.58 Hz, 4 H) 7.18 (s, 2 H). to exceed 30° C stirred for 1 h The mixture was extracted with hexanes (3×200 mL) washed with brine dried over Na2SO4 concentrated The crude oil was purified by flash chromatography (100% hexanes)

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2,6-diethyl-1-iodobenzene (10 g, 0.029 mol) in tetrahydrofuran (100 ml) at −75° C. is added n-butyl lithium (1.6 M in hexanes, 22.2 ml, 0.035 mol) dropwise maintaining the temperature of the reaction mixture below −70° C. When the addition is complete the mixture is stirred at −75° C. for an additional 30 minutes and then trimethyl borate (17.98 g, 0.17 mol) is added dropwise. After the addition is complete the reaction is stirred at −75° C. for 1 hour, then allowed to come to room temperature and stirred for 2 hours, followed by cooling in an ice bath and acidification with 0.5 N aqueous hydrochloric acid. The mixture is extracted with ethyl acetate (3×300 ml) and the organic fractions are combined, washed with brine, dried over anhydrous sodium sulphate. The mixture is filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethylphenylboronic acid (5 g) as a white solid. dropwise maintaining the temperature of the reaction mixture below −70° C When the addition After the addition is stirred at −75° C. for 1 hour to come to room temperature stirred for 2 hours by cooling in an ice bath The mixture is extracted with ethyl acetate (3×300 ml) washed with brine dried over anhydrous sodium sulphate The mixture is filtered the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica gel

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 4-bromo-2,6-diethylaniline (13.6 g, 0.06 mol) in distilled water (14 ml) is added concentrated sulphuric acid (14 ml), followed by brief heating to 60° C. for 1 hour until dissolution is complete. The mixture is allowed to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (4.1 g, 0.059 mol) in distilled water (20 ml) dropwise over 15 minutes, maintaining the temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is allowed to come to room temperature and then a solution of aqueous potassium iodide (29.8 g, 0.18 mol) in distilled water (30 ml) is added dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (150 ml×3) and the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml). The organic phase is dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethyl-1-iodobenzene (19 g) as an orange liquid. to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath maintaining the temperature below 5° C. to come to room temperature After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (150 ml×3) the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml) The organic phase is dried over anhydrous sodium sulphate concentrated under reduced pressure The residue is purified by column chromatography on silica gel