5-fluoro-2-hydroxy-3-methylbenzaldehyde

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 84 g of 4-fluoro-2-methylphenol are dissolved in 512 ml of trifluoroacetic acid and admixed with 181 g of hexamethylenetetramine in portions. On completion of addition, the reaction solution is heated to 100° C. for 5 hours. After cooling, first 80 ml of 50% sulphuric acid and then 480 ml of water are added dropwise, then the solution is stirred further at room temperature for 3 hours. The reaction solution is extracted three times with dichloromethane. The combined extracts are washed once with water and dried, and the solvent is distilled off under reduced pressure. The residue is extracted repeatedly with n-hexane, the extracts are combined and the solvent is distilled off under reduced pressure. The crude product is subsequently fractionally distilled. 25 g (25% of theory) of a bright yellow solid are obtained having a melting point of 49-52° C. and a boiling point of 70-72° C. at 7 mbar. On completion of addition After cooling The reaction solution is extracted three times with dichloromethane The combined extracts are washed once with water dried the solvent is distilled off under reduced pressure The residue is extracted repeatedly with n-hexane the solvent is distilled off under reduced pressure The crude product is subsequently fractionally distilled 25 g (25% of theory) of a bright yellow solid are obtained

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Fluoro-2-hydroxy-3-methylbenzaldehyde (1.24 g, 8.01 mmol) was dissolved in N,N-dimethylformamide (20 mL) and to the solution was added methyl iodide (0.8 mL, 12.71 mmol) and potassium carbonate (3.1 g, 22.52 mmol). The mixture was stirred at 100° C. for one hour, cooled to room temperature and then diluted with water (40 mL). After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine and then dried over Na2SO4. The solvent was removed and the solid residue was treated with methanol. After filtration and drying desired compound was obtained 1.2 g (99%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 1H), 7.23 (dd, 1H), 6.85 (dd, 1H), 3.75 (s, 3H), 2.32 (s, 3H). cooled to room temperature After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine dried over Na2SO4 The solvent was removed the solid residue was treated with methanol After filtration drying desired compound was obtained 1.2 g (99%)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Fluoro-2-hydroxy-3-methylbenzaldehyde (1.24 g, 8.01 mmol) was dissolved in N,N-dimethylformamide (20 mL) and to the solution was added methyl iodide (0.8 mL, 12.71 mmol) and potassium carbonate (3.1 g, 22.52 mmol). The mixture was stirred at 100° C. for one hour, cooled to room temperature and then diluted with water (40 mL). After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine and then dried over Na2SO4. The solvent was removed and the solid residue was treated with methanol. After filtration and drying desired compound was obtained 1.2 g (99%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 1H), 7.23 (dd, 1H), 6.85 (dd, 1H), 3.75 (s, 3H), 2.32 (s, 3H). cooled to room temperature After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine dried over Na2SO4 The solvent was removed the solid residue was treated with methanol After filtration drying desired compound was obtained 1.2 g (99%)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Fluoro-2-hydroxy-3-methylbenzaldehyde (1.24 g, 8.01 mmol) was dissolved in N,N-dimethylformamide (20 mL) and to the solution was added methyl iodide (0.8 mL, 12.71 mmol) and potassium carbonate (3.1 g, 22.52 mmol). The mixture was stirred at 100° C. for one hour, cooled to room temperature and then diluted with water (40 mL). After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine and then dried over Na2SO4. The solvent was removed and the solid residue was treated with methanol. After filtration and drying desired compound was obtained 1.2 g (99%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 1H), 7.23 (dd, 1H), 6.85 (dd, 1H), 3.75 (s, 3H), 2.32 (s, 3H). cooled to room temperature After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine dried over Na2SO4 The solvent was removed the solid residue was treated with methanol After filtration drying desired compound was obtained 1.2 g (99%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension containing 5-fluoro-2-hydroxy-3-methylbenzaldehyde (1.0 g, 6.49 mmol) and K2CO3 (980 mg, 7.10 mmol) in DMF (8 mL), bromoacetaldehyde diethyl acetal (1.10 mL, 7.15 mmol) was added dropwise. The mixture was refluxed for 4 h. After cooling, the precipitate was filtered off and the solvent was evaporated in vacuo. The crude residue was adsorbed on silica gel and purified by flash chromatography. The product was eluted with hexane/EtOAc (4:1) to give 20 (350 mg, 20%) as an oil, 1H NMR (500 MHz, CDCl3): δ: 10.40 (1H, s, CHO), 7.32 (1H, d, J=7.30 Hz, ArH), 7.14 (1H, d, J=7.75 Hz, ArH), 4.85 (1H, s, CH), 3.95 (2H, s, CH2), 3.75 (2H, t, J=7.15 Hz, CH2CH3), 3.61 (2H, t, J=7.20 Hz, CH2CH3), 2.36 (3H, s, CH3), 1.24 (6H, t, J=5.65 Hz, 2×CH3). was added dropwise The mixture was refluxed for 4 h After cooling the precipitate was filtered off the solvent was evaporated in vacuo purified by flash chromatography The product was eluted with hexane/EtOAc (4:1)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Fluoro-2-hydroxy-3-methylbenzaldehyde (1.24 g, 8.01 mmol) was dissolved in N,N-dimethylformamide (20 mL) and to the solution was added methyl iodide (0.8 mL, 12.71 mmol) and potassium carbonate (3.1 g, 22.52 mmol). The mixture was stirred at 100° C. for one hour, cooled to room temperature and then diluted with water (40 mL). After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine and then dried over Na2SO4. The solvent was removed and the solid residue was treated with methanol. After filtration and drying desired compound was obtained 1.2 g (99%). 1H NMR (400 MHz, CDCl3): δ10.12 (s, 1H), 7.23 (dd, 1H), 6.85 (dd, 1H), 3.75 (s, 3H), 2.32 (s, 3H). cooled to room temperature After extraction twice with ethyl acetate (40 mL) the combined organic layer was washed with brine dried over Na2SO4 The solvent was removed the solid residue was treated with methanol After filtration drying desired compound was obtained 1.2 g (99%)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 84 g of 4-fluoro-2-methylphenol are dissolved in 512 ml of trifluoroacetic acid and admixed with 181 g of hexamethylenetetramine in portions. On completion of addition, the reaction solution is heated to 100° C. for 5 hours. After cooling, first 80 ml of 50% sulphuric acid and then 480 ml of water are added dropwise, then the solution is stirred further at room temperature for 3 hours. The reaction solution is extracted three times with dichloromethane. The combined extracts are washed once with water and dried, and the solvent is distilled off under reduced pressure. The residue is extracted repeatedly with n-hexane, the extracts are combined and the solvent is distilled off under reduced pressure. The crude product is subsequently fractionally distilled. 25 g (25% of theory) of a bright yellow solid are obtained having a melting point of 49-52° C. and a boiling point of 70-72° C. at 7 mbar. On completion of addition After cooling The reaction solution is extracted three times with dichloromethane The combined extracts are washed once with water dried the solvent is distilled off under reduced pressure The residue is extracted repeatedly with n-hexane the solvent is distilled off under reduced pressure The crude product is subsequently fractionally distilled 25 g (25% of theory) of a bright yellow solid are obtained