4-bromo-2-methoxybenzaldehyde

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

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

Procedure: A mixture of 4-bromo-2-fluorobenzaldehyde (25.0 g, 0.123 mol) and sodium methoxide (13.99 g, 0.2600 mol) in dry methanol (250 mL) was stirred at reflux temperature for 16 hours. The mixture was concentrated and the residue was partitioned between dichloromethane (500 mL) and water (250 mL). The organic layers were combined and dried over sodium sulfate then concentrated in vacuo to provide the title compound as yellow solid (25 g, 94.5%). at reflux temperature for 16 hours The mixture was concentrated the residue was partitioned between dichloromethane (500 mL) and water (250 mL) dried over sodium sulfate then concentrated in vacuo

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: The mixture of 4-bromo-2-fluorobenzaldehyde (6.1 g, 0.03 mol) and sodium methoxide (1.78 g, 0.033 mol) in dry methanol (60 mL) was stirred at reflux for 16 hours. The methanol was evaporated. The residue was partitioned between DCM and water. The organic layers were dried over sodium sulfate, concentrated in vacuo to give a yellow solid, which was purified by silica gel chromatography (Petroleum ether/EtOAc=20:1 to 10:1) to give the title compound (6.3 g, 97%) as a light yellow solid. at reflux for 16 hours The methanol was evaporated The residue was partitioned between DCM and water The organic layers were dried over sodium sulfate concentrated in vacuo to give a yellow solid, which was purified by silica gel chromatography (Petroleum ether/EtOAc=20:1 to 10:1)

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

Procedure: A mixture of 4-bromo-2-fluorobenzaldehyde (25.0 g, 0.123 mol) and sodium methoxide (13.99 g, 0.2600 mol) in dry methanol (250 mL) was stirred at reflux temperature for 16 hours. The mixture was concentrated and the residue was partitioned between dichloromethane (500 mL) and water (250 mL). The organic layers were combined and dried over sodium sulfate then concentrated in vacuo to provide the title compound as yellow solid (25 g, 94.5%). at reflux temperature for 16 hours The mixture was concentrated the residue was partitioned between dichloromethane (500 mL) and water (250 mL) dried over sodium sulfate then concentrated in vacuo

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

Procedure: A mixture of 4-bromo-2-fluorobenzaldehyde (25.0 g, 0.123 mol) and sodium methoxide (13.99 g, 0.2600 mol) in dry methanol (250 mL) was stirred at reflux temperature for 16 hours. The mixture was concentrated and the residue was partitioned between dichloromethane (500 mL) and water (250 mL). The organic layers were combined and dried over sodium sulfate then concentrated in vacuo to provide the title compound as yellow solid (25 g, 94.5%). at reflux temperature for 16 hours The mixture was concentrated the residue was partitioned between dichloromethane (500 mL) and water (250 mL) dried over sodium sulfate then concentrated in vacuo

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 1H), 7.12 (d, 1H), 7.03 (s, 1H), 3.87 (s, 3H), 3.63 (s, 2H) heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 1H), 7.12 (d, 1H), 7.03 (s, 1H), 3.87 (s, 3H), 3.63 (s, 2H) heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: The mixture of 4-bromo-2-fluorobenzaldehyde (6.1 g, 0.03 mol) and sodium methoxide (1.78 g, 0.033 mol) in dry methanol (60 mL) was stirred at reflux for 16 hours. The methanol was evaporated. The residue was partitioned between DCM and water. The organic layers were dried over sodium sulfate, concentrated in vacuo to give a yellow solid, which was purified by silica gel chromatography (Petroleum ether/EtOAc=20:1 to 10:1) to give the title compound (6.3 g, 97%) as a light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 10.23 (s, 1H), 7.60 (d, 1H), 7.48 (s, 1H), 7.28 (d, 1H), 3.94 (s, 3H) at reflux for 16 hours The methanol was evaporated The residue was partitioned between DCM and water The organic layers were dried over sodium sulfate concentrated in vacuo to give a yellow solid, which was purified by silica gel chromatography (Petroleum ether/EtOAc=20:1 to 10:1)

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

Procedure: To a stirred solution of 4-bromo-2-fluorobenzaldehyde (96%, 3.38 g, 16.0 mmol) in methanol (35 mL) at ambient temperature was added a 25 wt % solution of sodium methoxide in methanol (4.02 mL, 17.6 mmol), and the resulting solution was stirred and heated to reflux for 2 hours. The solution was cooled to ambient temperature and concentrated, and the residue was partitioned between dichloromethane (100 mL) and water (50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 95/5 hexanes/ethyl acetate, to afford 4-bromo-2-methoxybenzaldehyde as a white solid (2.13 g, 62% yield). heated to reflux for 2 hours concentrated the residue was partitioned between dichloromethane (100 mL) and water (50 mL) The organic layer was dried over sodium sulfate concentrated The residue was purified by chromatography on silica gel eluting with 95/5 hexanes/ethyl acetate

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

Procedure: To a stirred solution of 4-bromo-2-fluorobenzaldehyde (96%, 3.38 g, 16.0 mmol) in methanol (35 mL) at ambient temperature was added a 25 wt % solution of sodium methoxide in methanol (4.02 mL, 17.6 mmol), and the resulting solution was stirred and heated to reflux for 2 hours. The solution was cooled to ambient temperature and concentrated, and the residue was partitioned between dichloromethane (100 mL) and water (50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 95/5 hexanes/ethyl acetate, to afford 4-bromo-2-methoxybenzaldehyde as a white solid (2.13 g, 62% yield). heated to reflux for 2 hours concentrated the residue was partitioned between dichloromethane (100 mL) and water (50 mL) The organic layer was dried over sodium sulfate concentrated The residue was purified by chromatography on silica gel eluting with 95/5 hexanes/ethyl acetate

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

Procedure: A suspension of 4-bromo-2-methoxybenzaldehyde (1.55 g; 7.2 mmol), methylamine hydrochloride (0.31 g; 50.4 mmol) and sodium acetate (0.38 g; 4.6 mmol) in 3 mL of nitromethane was stirred at ambient temperature. After stirring for 14.5 hours the mixture was diluted with 20 mL water and 40 mL dichloromethane, and the mixture was transferred to a separatory funnel. After shaking, the organic layer was dried over sodium sulfate and evaporated to give 1.74 g of 4-bromo-2-methoxy-1-(2-nitrovinyl)benzene as a light yellow solid. MS (apci, neg) m/z=257. After stirring for 14.5 hours the mixture the mixture was transferred to a separatory funnel After shaking the organic layer was dried over sodium sulfate evaporated