4-chloro-2-fluoro-5-methoxybenzaldehyde

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-2-fluoro-5-methoxy benzaldehyde (204 mg, 1.1 mmol) and 4-fluorophenylhydrazine (176 mg, 1.1 mmol) were dissolved in N-methylpyrrolidine (5 mL). After addition of cesium carbonate (1.15 g, 3.3 mmol) the mixture was heated in a microwave reactor (CEM Discovery, 150 Watt) to 150° C. for 20 min. After dilution with DCM the mixture was washed with sat. NaHCO3, brine and the organic phase was evaporated. After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained. After dilution with DCM the mixture was washed with sat. NaHCO3, brine the organic phase was evaporated After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-2-fluoro-5-methoxy benzaldehyde (204 mg, 1.1 mmol) and 4-fluorophenylhydrazine (176 mg, 1.1 mmol) were dissolved in N-methylpyrrolidine (5 mL). After addition of cesium carbonate (1.15 g, 3.3 mmol) the mixture was heated in a microwave reactor (CEM Discovery, 150 Watt) to 150° C. for 20 min. After dilution with DCM the mixture was washed with sat. NaHCO3, brine and the organic phase was evaporated. After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained. After dilution with DCM the mixture was washed with sat. NaHCO3, brine the organic phase was evaporated After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained

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

Procedure: A mixture of 36.3 g of 2-chloro-4-fluoro-5-iodo-1-methoxybenzene, 12.9 g of sodium formate, 1.78 g of dichlorobis(triphenylphosphine) palladium, and 113 ml of N,N-dimethylformamide was stirred, while bubbling carbon monoxide at 90° to 100° C. over 12 hours. After completion of the reaction, the reaction mixture was returned to room temperature, followed by dilution with diluted hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 7.09 g (yield, 30%) of 4-chloro-2-fluoro-5-methoxybenzaldehyde. while bubbling carbon monoxide at 90° to 100° C. over 12 hours After completion of the reaction was returned to room temperature the mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous magnesium sulfate concentrated

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

Procedure: A mixture of 36.3 g of 2-chloro-4-fluoro-5-iodo-1-methoxybenzene, 12.9 g of sodium formate, 1.78 g of dichlorobis(triphenylphosphine) palladium, and 113 ml of N,N-dimethylformamide was stirred, while bubbling carbon monoxide at 90° to 100° C. over 12 hours. After completion of the reaction, the reaction mixture was returned to room temperature, followed by dilution with diluted hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 7.09 g (yield, 30%) of 4-chloro-2-fluoro-5-methoxybenzaldehyde. while bubbling carbon monoxide at 90° to 100° C. over 12 hours After completion of the reaction was returned to room temperature the mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous magnesium sulfate concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-2-fluoro-5-methoxybenzaldehyde (0.821 g, 4.35 mmol) in 8.7 mL of DMSO were successively added K2CO3 (1.81 g, 3 eq.) and methyl thioglycolate (0.474 mL, 1.2 eq.), and the mixture was vigorously stirred at 50° C. for 2 h. After cooling, the reaction mixture was poured onto crashed ice/HCl, twofold extracted with AcOEt, washed with water, dried over sodium sulfate, and evaporated. Flash chromatography (SiO2, hexane/AcOEt=85/15), followed by crystallization from heptane/AcOEt, yielded 0.300 g of the title compound as off-white solid. After cooling the reaction mixture was poured twofold extracted with AcOEt washed with water dried over sodium sulfate evaporated Flash chromatography (SiO2, hexane/AcOEt=85/15), followed by crystallization from heptane/AcOEt

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-2-fluoro-5-methoxy benzaldehyde (204 mg, 1.1 mmol) and 4-fluorophenylhydrazine (176 mg, 1.1 mmol) were dissolved in N-methylpyrrolidine (5 mL). After addition of cesium carbonate (1.15 g, 3.3 mmol) the mixture was heated in a microwave reactor (CEM Discovery, 150 Watt) to 150° C. for 20 min. After dilution with DCM the mixture was washed with sat. NaHCO3, brine and the organic phase was evaporated. After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained. After dilution with DCM the mixture was washed with sat. NaHCO3, brine the organic phase was evaporated After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained

Conditions: temp:22.01; pressure:0.00; stir:

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-2-fluoro-5-methoxy benzaldehyde (204 mg, 1.1 mmol) and 4-fluorophenylhydrazine (176 mg, 1.1 mmol) were dissolved in N-methylpyrrolidine (5 mL). After addition of cesium carbonate (1.15 g, 3.3 mmol) the mixture was heated in a microwave reactor (CEM Discovery, 150 Watt) to 150° C. for 20 min. After dilution with DCM the mixture was washed with sat. NaHCO3, brine and the organic phase was evaporated. After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained. After dilution with DCM the mixture was washed with sat. NaHCO3, brine the organic phase was evaporated After purification of the crude by flash chromatography on silica gel 253 mg (84%) of the subtitle compound were obtained