3-FLUORO-2-METHOXYBENZALDEHYDE

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: To a solution of 3-fluoro-2-methoxy-benzaldehyde (3.41 g, 22.1 mmol) in methanol (20 mL) is slowly added portionwise sodium borohydride (1.00 g, 26.6 mmol). The reaction is stirred at room temperature under nitrogen overnight. The reaction is diluted with diethyl ether, washed with water twice, dried over anhydrous sodium sulfate, filtered, and concentrated to afford 3.02 g (87%) of the title compound as a clear colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.09-6.92 (m, 3H), 4.65 (d, 2H), 3.97 (s, 3H), 2.14 (t, 1H, OH). washed with water twice dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: A mixture of 3-fluorosalicylaldehyde (3.52 g, 25.12 mmol) and cesium carbonate (20.46 g, 62.81 mmol) in N,N-dimethylformamide (30 mL) is treated with iodomethane (3.13 mL, 50.2 mmol) and stirred at room temperature under nitrogen for 2 h. The reaction mixture is diluted with diethyl ether (150 mL) and washed with 0.5 M hydrochloric acid (2×150 mL). The organic portion is dried over anhydrous sodium sulfate, filtered, and concentrated to afford 3.42 g (88%) of the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, 1H), 7.32 (dd, 1H), 7.04 (m, 1H), 4.04 (s, 3H). washed with 0.5 M hydrochloric acid (2×150 mL) The organic portion is dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: A mixture of 3-fluorosalicylaldehyde (3.52 g, 25.12 mmol) and cesium carbonate (20.46 g, 62.81 mmol) in N,N-dimethylformamide (30 mL) is treated with iodomethane (3.13 mL, 50.2 mmol) and stirred at room temperature under nitrogen for 2 h. The reaction mixture is diluted with diethyl ether (150 mL) and washed with 0.5 M hydrochloric acid (2×150 mL). The organic portion is dried over anhydrous sodium sulfate, filtered, and concentrated to afford 3.42 g (88%) of the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, 1H), 7.32 (dd, 1H), 7.04 (m, 1H), 4.04 (s, 3H). washed with 0.5 M hydrochloric acid (2×150 mL) The organic portion is dried over anhydrous sodium sulfate filtered concentrated

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

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an acetonitrile (50 mL) solution containing 3.01 g (21.5 mmol) of commercially available 3-fluoro-2-hydroxybenzaldehyde were added 5.92 g (42.8 mmol) of potassium carbonate and 6.66 mL (107 mmol) of methyl iodide, and the mixture was stirred at 90° C. for 3 hours. After allowing to stand at room temperature overnight, the reaction mixture was poured into water, and extracted with ethyl acetate. The organic layer was successively washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed, and the obtained residue was purified by silica gel column chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to obtain 3.22 g of a crude product of 3-fluoro-2-methoxybenzaldehyde. to stand at room temperature overnight extracted with ethyl acetate The organic layer was successively washed with water and brine dried over anhydrous magnesium sulfate The solvent was removed the obtained residue was purified by silica gel column chromatography (Wako gel C-100, hexane-ethyl acetate, gradient)

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

Procedure: To a suspension of 3-fluoro-2-hydroxybenzaldehyde (5.328 g, 38.02 mmol) and potassium carbonate (7.88 g, 57.03 mmol) in acetone (60 mL) was added dimethyl sulphate (3.96 mL, 41.83 mmol). The resulting suspension was stirred at 60° C. for 2 h before being allowed to cool and then concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and water (50 mL). The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) and the solvent evaporated in vacuo to give a pale yellow oil (6.262 g, 38.02 mmol, 100%). δH (300 MHz, CDCl3) 10.40 (1H, s, CHO), 7.60 (1H, d, Ar), 7.30 (1H, m, Ar), 7.10 (1H, m, Ar), 4.10 (3H, s, OCH3). to cool concentrated in vacuo The residue was dissolved in dichloromethane (100 mL) The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) the solvent evaporated in vacuo

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

Procedure: To a suspension of 3-fluoro-2-hydroxybenzaldehyde (5.328 g, 38.02 mmol) and potassium carbonate (7.88 g, 57.03 mmol) in acetone (60 mL) was added dimethyl sulphate (3.96 mL, 41.83 mmol). The resulting suspension was stirred at 60° C. for 2 h before being allowed to cool and then concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and water (50 mL). The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) and the solvent evaporated in vacuo to give a pale yellow oil (6.262 g, 38.02 mmol, 100%). δH (300 MHz, CDCl3) 10.40 (1H, s, CHO), 7.60 (1H, d, Ar), 7.30 (1H, m, Ar), 7.10 (1H, m, Ar), 4.10 (3H, s, OCH3). to cool concentrated in vacuo The residue was dissolved in dichloromethane (100 mL) The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) the solvent evaporated in vacuo

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

Procedure: To a suspension of 3-fluoro-2-hydroxybenzaldehyde (5.328 g, 38.02 mmol) and potassium carbonate (7.88 g, 57.03 mmol) in acetone (60 mL) was added dimethyl sulphate (3.96 mL, 41.83 mmol). The resulting suspension was stirred at 60° C. for 2 h before being allowed to cool and then concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and water (50 mL). The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) and the solvent evaporated in vacuo to give a pale yellow oil (6.262 g, 38.02 mmol, 100%). δH (300 MHz, CDCl3) 10.40 (1H, s, CHO), 7.60 (1H, d, Ar), 7.30 (1H, m, Ar), 7.10 (1H, m, Ar), 4.10 (3H, s, OCH3). to cool concentrated in vacuo The residue was dissolved in dichloromethane (100 mL) The organic phase was washed with saturated sodium bicarbonate (50 mL) with the resulting organic phase being dried (MgSO4) the solvent evaporated in vacuo