3,5-二氟-4-苄氧基苯甲醛

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1,2-diethoxy-2-oxoethyl)triphenylphosphonium chloride (679) (1.61 g, 3.76 mmol) in tetrahydrofuran (56 mL) was added DBU (0.67 ml, 4.51 mmol) and the reaction was stirred for 10 minutes at room temperature. 4-(benzyloxy)-3,5-difluorobenzaldehyde (1.40 g, 5.64 mmol) was added in one portion and the reaction was stirred at room temperature for 18 hours. The solvent was removed in vacuo, diethyl ether was added and the solids filtered. The filtrate was concentrated in vacuo and the residue oil was purified by flash column chromatography (0-30% EtOAc in hexanes) to provide (Z)-ethyl 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-ethoxyacrylate (680). the reaction was stirred at room temperature for 18 hours The solvent was removed in vacuo, diethyl ether was added the solids filtered The filtrate was concentrated in vacuo the residue oil was purified by flash column chromatography (0-30% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1,2-diethoxy-2-oxoethyl)triphenylphosphonium chloride (679) (1.61 g, 3.76 mmol) in tetrahydrofuran (56 mL) was added DBU (0.67 ml, 4.51 mmol) and the reaction was stirred for 10 minutes at room temperature. 4-(benzyloxy)-3,5-difluorobenzaldehyde (1.40 g, 5.64 mmol) was added in one portion and the reaction was stirred at room temperature for 18 hours. The solvent was removed in vacuo, diethyl ether was added and the solids filtered. The filtrate was concentrated in vacuo and the residue oil was purified by flash column chromatography (0-30% EtOAc in hexanes) to provide (Z)-ethyl 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-ethoxyacrylate (680). the reaction was stirred at room temperature for 18 hours The solvent was removed in vacuo, diethyl ether was added the solids filtered The filtrate was concentrated in vacuo the residue oil was purified by flash column chromatography (0-30% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-(benzyloxy)-3,5-difluorobenzaldehyde (7) (1.32 g, 5.34 mmol) and (1-ethoxycarbonylethylidene)triphenyl phosphorane (2.32 g, 6.41 mmol) in tetrahydrofuran (53 mL) was refluxed for 2 hours. The reaction was concentrated in vacuo and was purified by flash column chromatography (0-100% EtOAc in hexanes) to give (E)-ethyl 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylacrylate (8). The reaction was concentrated in vacuo was purified by flash column chromatography (0-100% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-(benzyloxy)-3,5-difluorobenzaldehyde (7) (1.32 g, 5.34 mmol) and (1-ethoxycarbonylethylidene)triphenyl phosphorane (2.32 g, 6.41 mmol) in tetrahydrofuran (53 mL) was refluxed for 2 hours. The reaction was concentrated in vacuo and was purified by flash column chromatography (0-100% EtOAc in hexanes) to give (E)-ethyl 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylacrylate (8). The reaction was concentrated in vacuo was purified by flash column chromatography (0-100% EtOAc in hexanes)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 3,5-difluoro-4-hydroxybenzaldehyde (6) (8.26 g, 52.2 mmol), and potassium carbonate (14.4 g, 104.4 mmol) in dimethylformamide (100 mL) was added benzyl chloride (7.2 mL, 62.7 mmol) and stirred overnight at 50° C. The reaction was diluted with water and extracted with ethyl acetate (3×75 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes) to afford 4-(benzyloxy)-3,5-difluorobenzaldehyde (7). extracted with ethyl acetate (3×75 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash column chromatography on silica gel (0-100% EtOAc in hexanes)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: After methoxymethyl triphenyl phosphonium chloride (1.04 g, 3.02 mmol) was dissolved in anhydrous THF (9 mL), LiHMDS 1.0M THF solution (3 mL, 3.02 mmol) was added thereto at 0° C., and the mixture was stirred for 15 minutes. 4-Benzyloxy-3,5-difluoro-benzaldehyde (0.50 g, 2.01 mmol) obtained in Step B of Preparation Example 2 was dissolved in anhydrous THF (6 mL), and the solution was added thereto. The mixture was stirred at room temperature for 3 hours. After the termination of the reaction, the reactant was added with water, and then extracted with EtOAc. The organic layer was separated, dried with MgSO4, concentrated under reduced pressure, and then purified by column chromatography (eluent, EtOAc/Hex=1/5). After the obtained product was dissolved in THF (7.68 mL), 2N HCl (3.84 mL) was added thereto, and the mixture was stirred at 70° C. for 5 hours. After the termination of the reaction, the reactant was concentrated under reduced pressure, added with water, and then extracted with EtOAc. The organic layer was separated, dried with MgSO4, concentrated under reduced pressure, and the purified by column chromatography (eluent, EtOAc/Hex=1/5) to obtain the title compound (0.107 g, 20%). the solution was added The mixture was stirred at room temperature for 3 hours After the termination of the reaction extracted with EtOAc The organic layer was separated dried with MgSO4 concentrated under reduced pressure purified by column chromatography (eluent, EtOAc/Hex=1/5) After the obtained product was dissolved in THF (7.68 mL) 2N HCl (3.84 mL) was added the mixture was stirred at 70° C. for 5 hours After the termination of the reaction the reactant was concentrated under reduced pressure added with water extracted with EtOAc The organic layer was separated dried with MgSO4 concentrated under reduced pressure the purified by column chromatography (eluent, EtOAc/Hex=1/5)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Benzyloxy-3,5-difluoro-benzaldehyde (1.2 g, 4.83 mmol) obtained in Step B and carbethoxymethylene triphenylphosphorane (2.0 g, 5.78 mmol) was dissolved in THF (10 mL), and the solution was stirred at 65˜75° C. for 1 hour. After the termination of the reaction, the reactant was cooled and concentrated under reduced pressure. The residue was purified by column chromatography (eluent, EtOAc/Hex=1/10) to obtain the title compound (1.2 g, 78%). After the termination of the reaction the reactant was cooled concentrated under reduced pressure The residue was purified by column chromatography (eluent, EtOAc/Hex=1/10)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3,5-Difluoro-4-hydroxy-benzaldehyde obtained in Step A was dissolved in CH3CN (15 mL), and Cs2CO3(6.3 g, 19.23 mmol) was added to the solution. The mixture was cooled to 0˜5° C. Benzylbromide (1.1 mL, 9.23 mmol) was added slowly thereto, and the mixture was stirred at room temperature for 2 hours. After the termination of the reaction, the reactant was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (eluent, EtOAc/Hex=1/7) to obtain the title compound (1.76 g, 92%). The mixture was cooled to 0˜5° C After the termination of the reaction the reactant was filtered concentrated under reduced pressure The residue was purified by column chromatography (eluent, EtOAc/Hex=1/7)

反应条件: temp:22.01; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir: