1,3-dibromo-5-fluoro-2-iodobenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled to −35° C. was added the solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0 M in diethyl ether) over a period of 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained. Stirring was continued for 1.5 h. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The temperature of the reaction mixture increased to −19° C. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. The reaction was quenched with saturated aqueous NH4Cl (100 mL), filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1) to give 102a (20 g, yield 54%) as a yellow solid. while maintaining the internal temperature below −25° C A clear brown solution was obtained The reaction mixture was warmed to 10° C. (room temperature) over 1 h stirred at this temperature for 1.5 h The reaction was quenched with saturated aqueous NH4Cl (100 mL) filtered evaporated under reduced pressure The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added a solution of isopropyl-magnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h (hours). It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 104k as a white solid (20 g, 54%). 1H NMR (500 MHz, CDCl3) δ 10.23 (s, 1H), 7.48 (d, J=7.5, 2H). while maintaining the internal temperature below −25° C A clear brown solution was obtained It was then quenched with 3.0M HCl followed by the addition of ethyl acetate The organic layer was separated evaporated under reduced pressure The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added a solution of isopropyl-magnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h (hours). It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 104k as a white solid (20 g, 54%). 1H NMR (500 MHz, CDCl3) δ 10.23 (s, 1H), 7.48 (d, J=7.5, 2H). while maintaining the internal temperature below −25° C A clear brown solution was obtained It was then quenched with 3.0M HCl followed by the addition of ethyl acetate The organic layer was separated evaporated under reduced pressure The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)

反応条件: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) was cooled to −35° C. A solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0 M in diethyl ether) over a period of 30 minutes while maintaining the internal temperature below −25° C. See FIG. 1. A clear brown solution was obtained. Stirring was continued for 1.5 h. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The temperature of the reaction mixture increased to −19° C. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. The reaction was quenched with saturated aqueous NH4Cl (100 mL), filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate:from 50:1 to 20:1) to give 101a (20 g, yield 54%) as a yellow solid. A clear brown solution was obtained The reaction mixture was warmed to 10° C. (room temperature) over 1 h stirred at this temperature for 1.5 h The reaction was quenched with saturated aqueous NH4Cl (100 mL) filtered evaporated under reduced pressure The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate:from 50:1 to 20:1)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added the solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 101h as a white solid (20 g, 54%). while maintaining the internal temperature below −25° C A clear brown solution was obtained It was then quenched with 3.0M HCl followed by the addition of ethyl acetate The organic layer was separated evaporated under reduced pressure The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added the solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 101h as a white solid (20 g, 54%). while maintaining the internal temperature below −25° C A clear brown solution was obtained It was then quenched with 3.0M HCl followed by the addition of ethyl acetate The organic layer was separated evaporated under reduced pressure The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added a solution of isopropyl-magnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h (hours). It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 104k as a white solid (20 g, 54%). 1H NMR (500 MHz, CDCl3) δ 10.23 (s, 1H), 7.48 (d, J=7.5, 2H). while maintaining the internal temperature below −25° C A clear brown solution was obtained It was then quenched with 3.0M HCl followed by the addition of ethyl acetate The organic layer was separated evaporated under reduced pressure The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)

反応条件: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) was cooled to −35° C. A solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0 M in diethyl ether) over a period of 30 minutes while maintaining the internal temperature below −25° C. See FIG. 1. A clear brown solution was obtained. Stirring was continued for 1.5 h. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The temperature of the reaction mixture increased to −19° C. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. The reaction was quenched with saturated aqueous NH4Cl (100 mL), filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1) to give 101a (20 g, yield 54%) as a yellow solid. A clear brown solution was obtained The reaction mixture was warmed to 10° C. (room temperature) over 1 h stirred at this temperature for 1.5 h The reaction was quenched with saturated aqueous NH4Cl (100 mL) filtered evaporated under reduced pressure The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1)

反応条件: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled to −35° C. was added the solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0 M in diethyl ether) over a period of 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained. Stirring was continued for 1.5 h. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The temperature of the reaction mixture increased to −19° C. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. The reaction was quenched with saturated aqueous NH4Cl (100 mL), filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1) to give 102a (20 g, yield 54%) as a yellow solid. while maintaining the internal temperature below −25° C A clear brown solution was obtained The reaction mixture was warmed to 10° C. (room temperature) over 1 h stirred at this temperature for 1.5 h The reaction was quenched with saturated aqueous NH4Cl (100 mL) filtered evaporated under reduced pressure The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1)

反応条件: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled to −35° C. was added the solution of isopropylmagnesium chloride (84 mL, 171 mmol, 2.0 M in diethyl ether) over a period of 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained. Stirring was continued for 1.5 h. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The temperature of the reaction mixture increased to −19° C. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h. The reaction was quenched with saturated aqueous NH4Cl (100 mL), filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1) to give 102a (20 g, yield 54%) as a yellow solid. while maintaining the internal temperature below −25° C A clear brown solution was obtained The reaction mixture was warmed to 10° C. (room temperature) over 1 h stirred at this temperature for 1.5 h The reaction was quenched with saturated aqueous NH4Cl (100 mL) filtered evaporated under reduced pressure The residue was purified by silica-gel column chromatography (eluting with petroleum ether/ethyl acetate: from 50:1 to 20:1)

反応条件: temp:0.00; pressure:0.00; stir: