5-(dimethoxymethyl)-2-fluorobenzaldehyde

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

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

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

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: A total of 1.08 g of benzothiazole was dissolved in 15 ml of dry tetrahydrofuran. After cooling to −78° C. in an atmosphere of nitrogen gas, 6.4 ml of 1.56 M solution of n-butyllithium in hexane was added. After stirring for 5 minutes, 8 ml of a solution of 1.35 g of 5-(dimethoxymethyl)-2-fluorobenzaldehyde in dry tetrahydrofuran was added, followed by stirring for 10 minutes. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate for two times. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=3:7), to give 1.8 g of the title compound as a yellow oil. was added by stirring for 10 minutes the mixture was extracted with ethyl acetate for two times The organic layer was washed with water dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=3:7)

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

Procedure: A total of 1.08 g of benzothiazole was dissolved in 15 ml of dry tetrahydrofuran. After cooling to −78° C. in an atmosphere of nitrogen gas, 6.4 ml of 1.56 M solution of n-butyllithium in hexane was added. After stirring for 5 minutes, 8 ml of a solution of 1.35 g of 5-(dimethoxymethyl)-2-fluorobenzaldehyde in dry tetrahydrofuran was added, followed by stirring for 10 minutes. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate for two times. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=3:7), to give 1.8 g of the title compound as a yellow oil. was added by stirring for 10 minutes the mixture was extracted with ethyl acetate for two times The organic layer was washed with water dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=3:7)

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

Procedure: A total of 2.49 g of 3-bromo-4-fluorobenzaldehyde dimethylacetal produced in Production Example I-4-a was dissolved in 20 ml of dry tetrahydrofuran. After cooling to −78° C. in an atmosphere of nitrogen gas, 8.5 ml of a 1.56 M solution of n-butyllithium in hexane was added. After stirring for 30 minutes, 1.0 ml of N,N-dimethylformamide was added and the mixture was heated to room temperature. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate for two times. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:12.5), to give 1.35 g of the title compound as a colorless oil. was added the mixture was extracted with ethyl acetate for two times The organic layer was washed with water dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=1:12.5)

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

Procedure: 2.8 g of 5-Dimethoxymethyl-2-fluorobenzaldehyde was dissolved in 40 ml of diethyl ether, and 0.38 g of lithium aluminum hydride was added under ice-cooling. After being stirred at room temperature for 5 minutes, the reaction solution was ice-cooled and diethylether-water was added. When the insoluble precipitate adhered to the wall of the flask, the reaction solution was dried over anhydrous magnesium sulfate, then evaporated. The residue was dissolved in 25 ml of dichloromethane, and 8 ml of trifluoroacetic acid was added. The reaction mixture was stirred at room temperature for 2.5 hours, the reaction solution was diluted with water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then evaporated. The residue was subjected to silica gel column chromatography (30% ethyl acetate-hexane), to give 1.6 g of the title compound. cooling cooled the reaction solution was dried over anhydrous magnesium sulfate evaporated The residue was dissolved in 25 ml of dichloromethane 8 ml of trifluoroacetic acid was added The reaction mixture was stirred at room temperature for 2.5 hours the reaction solution was diluted with water the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate evaporated

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.2 g of 2-Bromo-4-dimethoxymethyl-1-fluorobenzene was dissolved in 65 ml of tetrahydrofuran, and the solution was cooled to −60° C. under a nitrogen gas flow. 18 ml of 1.6M n-Butyl lithium in hexane was added dropwise and the mixture was stirred at −60° C. for 1 hour. 3.3 ml of N-Formylmorpholine was added thereto, and the reaction mixture was allowed to warm to room temperature. The mixture was stirred for 1 hour, then ice-cooled, and treated with water and ammonium chloride solution, then extracted with ethylacetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was subjected to silica gel column chromatography, to give 2.8 g of the title compound (8% ethyl acetate-hexane). to warm to room temperature The mixture was stirred for 1 hour ice-cooled extracted with ethylacetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate evaporated

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

Procedure: A total of 1.08 g of benzothiazole was dissolved in 15 ml of dry tetrahydrofuran. After cooling to −78° C. in an atmosphere of nitrogen gas, 6.4 ml of 1.56 M solution of n-butyllithium in hexane was added. After stirring for 5 minutes, 8 ml of a solution of 1.35 g of 5-(dimethoxymethyl)-2-fluorobenzaldehyde in dry tetrahydrofuran was added, followed by stirring for 10 minutes. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate for two times. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=3:7), to give 1.8 g of the title compound as a yellow oil. was added by stirring for 10 minutes the mixture was extracted with ethyl acetate for two times The organic layer was washed with water dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=3:7)

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

Procedure: A total of 2.49 g of 3-bromo-4-fluorobenzaldehyde dimethylacetal produced in Production Example I-4-a was dissolved in 20 ml of dry tetrahydrofuran. After cooling to −78° C. in an atmosphere of nitrogen gas, 8.5 ml of a 1.56 M solution of n-butyllithium in hexane was added. After stirring for 30 minutes, 1.0 ml of N,N-dimethylformamide was added and the mixture was heated to room temperature. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate for two times. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:12.5), to give 1.35 g of the title compound as a colorless oil. was added the mixture was extracted with ethyl acetate for two times The organic layer was washed with water dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified separated by silica gel column chromatography (ethyl acetate:hexane=1:12.5)