1,5-dibromo-2,4-difluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using analogous reagents and reaction conditions as described in Example 27 for the preparation of I-27a above, 1,5-dibromo-2,4-difluorobenzene (3 g, 11.07 mmol) in dry ether was reacted with DMF (1.05 mL, 14.39 mmol) and n-butyl lithium (6.08 ml, 11.56 mmol to afford the crude product. Purification by column chromatography on silica gel (2% ethyl acetate in hexane) afforded 1.5 g of the product (61% yield). reagents and reaction conditions to afford the crude product Purification by column chromatography on silica gel (2% ethyl acetate in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using analogous reagents and reaction conditions as described in Example 27 for the preparation of I-27a above, 1,5-dibromo-2,4-difluorobenzene (3 g, 11.07 mmol) in dry ether was reacted with DMF (1.05 mL, 14.39 mmol) and n-butyl lithium (6.08 ml, 11.56 mmol to afford the crude product. Purification by column chromatography on silica gel (2% ethyl acetate in hexane) afforded 1.5 g of the product (61% yield). reagents and reaction conditions to afford the crude product Purification by column chromatography on silica gel (2% ethyl acetate in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As a raw material, 17.7 g of 1,5-dibromo-2,4-difluorobenzene obtained in Production Example II-5-a was subjected to lithiation with n-butyllithium by the procedure of Production Example II-5-b, was subjected to formylation with N,N-dimethylformamide, to give 10.7 g of 5-bromo-2,4-difluorobenzaldehyde. This compound was allowed to react with benzothiophene by the procedure of Production Example II-12-a to yield an alcohol, and then the alcohol was oxidized by the procedure of Production Example II-10-b, to give 9.7 g of the title compound as a colorless oil.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As a raw material, 17.7 g of 1,5-dibromo-2,4-difluorobenzene obtained in Production Example II-5-a was subjected to lithiation with n-butyllithium by the procedure of Production Example II-5-b, was subjected to formylation with N,N-dimethylformamide, to give 10.7 g of 5-bromo-2,4-difluorobenzaldehyde. This compound was allowed to react with benzothiophene by the procedure of Production Example II-12-a to yield an alcohol, and then the alcohol was oxidized by the procedure of Production Example II-10-b, to give 9.7 g of the title compound as a colorless oil.

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A total of 2.02 g of 1,5-dibromo-2,4-difluorobenzene obtained in Production Example II-5-a was dissolved in 38 ml of diethyl ether, and 4.9 ml of a 1.58 M solution of n-butyllithium in hexane was added under stirring at −70° C. After stirring for 1 hour, 4.9 ml of m-fluorobenzaldehyde was added and the mixture was stirred for 15 minutes. Saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extracting with ethyl acetate. The resulting organic layer was washed with brine, dried over magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:10), to give 0.96 g of the title compound. After stirring for 1 hour the mixture was stirred for 15 minutes by extracting with ethyl acetate The resulting organic layer was washed with brine dried over magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=1:10)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A total of 1.6 g of 1-bromo-2,4-difluorobenzene was suspended in 8.29 ml of sulfuric acid, and 1.62 g of N-bromosuccinimide was added under ice-cooling. After stirring at room temperature for 17 hours, the reaction mixture was poured onto ice-water and extracted with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (hexane), to give 2.18 g of the title compound as a pale yellow oil. cooling the reaction mixture was poured onto ice-water extracted with ethyl acetate The resulting organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and brine dried over magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A total of 1.6 g of 1-bromo-2,4-difluorobenzene was suspended in 8.29 ml of sulfuric acid, and 1.62 g of N-bromosuccinimide was added under ice-cooling. After stirring at room temperature for 17 hours, the reaction mixture was poured onto ice-water and extracted with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (hexane), to give 2.18 g of the title compound as a pale yellow oil. cooling the reaction mixture was poured onto ice-water extracted with ethyl acetate The resulting organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and brine dried over magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under ice cooling, a solution of 25.35 g of 1-bromo-2,4-difluorobenzene in 100 mL of concentrated sulfuric acid was added with 25.7 g of N-bromosuccinimide, and stirred for 30 minutes at this temperature and for 2 days at room temperature. After cooling on ice, the reaction solution was added with ice, and extracted with 300 mL of diethyl ether. The organic layer was successively washed with water, saturated aqueous sodium hydrogen carbonate and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting crude product was purified and separated by silica gel column chromatography (n-hexane), to afford 34.6 g of the title compound as a colorless oil. After cooling on ice the reaction solution was added with ice extracted with 300 mL of diethyl ether The organic layer was successively washed with water, saturated aqueous sodium hydrogen carbonate and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated the resulting crude product was purified separated by silica gel column chromatography (n-hexane)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: