5-bromo-2,4-difluorobenzaldehyde

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 reaction condition and reagents as described in Example 25 for the preparation of I-25a above, 5-bromo-2,4-difluorobenzaldehyde (I-28a: 475 mg, 2.149 mmol) was reacted with TEA (0.748 mL, 5.372 mmol), mercapto-acetic acid methyl ester (0.211 mL, 2.36 mmol) and DMSO (4 mL) to afford crude product. Purification by column chromatography on silica gel (1.5% ethyl acetate in hexane) afforded 30 mg of the product (5% yield). to afford crude product Purification by column chromatography on silica gel (1.5% ethyl acetate in hexane)

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

Procedure: Using analogous reaction condition and reagents as described in Example 25 for the preparation of I-25a above, 5-bromo-2,4-difluorobenzaldehyde (I-28a: 475 mg, 2.149 mmol) was reacted with TEA (0.748 mL, 5.372 mmol), mercapto-acetic acid methyl ester (0.211 mL, 2.36 mmol) and DMSO (4 mL) to afford crude product. Purification by column chromatography on silica gel (1.5% ethyl acetate in hexane) afforded 30 mg of the product (5% yield). to afford crude product Purification by column chromatography on silica gel (1.5% 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: Using analogous reaction condition and reagents as described in Example 25 for the preparation of I-25a above, 5-bromo-2,4-difluorobenzaldehyde (I-28a: 475 mg, 2.149 mmol) was reacted with TEA (0.748 mL, 5.372 mmol), mercapto-acetic acid methyl ester (0.211 mL, 2.36 mmol) and DMSO (4 mL) to afford crude product. Purification by column chromatography on silica gel (1.5% ethyl acetate in hexane) afforded 30 mg of the product (5% yield). to afford crude product Purification by column chromatography on silica gel (1.5% 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:0.00; pressure:0.00; stir:

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.6 M solution of butyl lithium in hexane (114 mL, 182 mmol) is added to a −78° C. solution of 1,5-dibromo-2,4-difluorobenzene (41.3 g, 152 mmol) in diethyl ether (290 mL). Dimethylformamide (14.4 g, 198 mmol) is added and the reaction is stirred at −78° C. for 15 minutes. The reaction is quenched with 1 N HCl (300 mL), is diluted with water, and extracted three times with ethyl acetate. The organic layer is dried over sodium sulfate and the solvent is removed under reduced pressure to give crude material that is purified by silica gel chromatography with a linear gradient of 0% to 50% CH2Cl2 in hexanes over 30 minutes to give the title compound (20.51 g, 61%). GC-MS m/e (79Br/81Br) 220, 222. The reaction is quenched with 1 N HCl (300 mL) is diluted with water extracted three times with ethyl acetate The organic layer is dried over sodium sulfate the solvent is removed under reduced pressure to give crude material that is purified by silica gel chromatography with a linear gradient of 0% to 50% CH2Cl2 in hexanes over 30 minutes