4-fluoro-2-methoxybenzaldehyde

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

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

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methoxide solution (25% by weight in methanol, 22.25 mL) and methanol (52 mL) were added to a flask and cooled to −20° C. using an acetonitrile/dry ice bath. Ethyl 2-azidoacetate (25% by weight in ethanol, 50.3 g) and 4-fluoro-2-methoxybenzaldehyde (5.00 g, dissolved in ethyl 2-azidoacetate solution) were added drop-wise to the stirring sodium methoxide solution at −20° C. The solution was then stirred at −20° C. for 3.5 hours, then at 0° C. for one hour. The solution was poured over ice, vacuum filtered, and washed with water. The filtered solid was taken up in xylenes (100 mL), washed twice with brine, and dried using anhydrous sodium sulfate and filtered. In a separate flask xylenes (50 mL) was brought to reflux. The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes. The solution was then refluxed for five hours, cooled, and placed in a freezer for 16 hours. The precipitate was filtered out. The volume of the filtrate was reduced on vacuum to generate a second crop of precipitate, which was washed with hexanes, then 5% ethyl acetate in hexanes and combined with material from the first filtration. at 0° C. for one hour The solution was poured over ice, vacuum filtered washed with water washed twice with brine dried filtered In a separate flask xylenes (50 mL) was brought to reflux The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes The solution was then refluxed for five hours cooled placed in a freezer for 16 hours The precipitate was filtered out was washed with hexanes 5% ethyl acetate in hexanes and combined with material from the first filtration

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

Procedure: Following the procedure used to prepare 1-(2,6-dimethoxy-pyridin-3-yl)-3-phenyl-prop-2-yn-1-ol, 4-fluoro-2-methoxy-benzaldehyde was reacted to give the title compound (1.60 g, 96%) as a colourless oil. LCMS (Method A): RT=4.30 min, [M+Na]+=279. was reacted

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

Procedure: Following the procedure used to prepare 1-(2,6-dimethoxy-pyridin-3-yl)-3-phenyl-prop-2-yn-1-ol, 4-fluoro-2-methoxy-benzaldehyde was reacted to give the title compound (1.60 g, 96%) as a colourless oil. LCMS (Method A): RT=4.30 min, [M+Na]+=279. was reacted

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

Procedure: An ice-cold solution of 5.6 g of 4-fluoro-2-methoxy-benzaldehyde in 75 ml of methanol was treated portionwise (5 portions within 50 minutes) with 1.51 g (40 mmol) of sodium borohydride and the reaction mixture was stirred for another 1 hour at room temperature. A dispersion of 7 g of potassium hydrogencarbonate in 20 ml of water was added and the mixture stirred for 30 minutes at room temperature. Thereupon, most of the methanol was evaporated under reduced pressure and the residue extracted with dichloromethane. The organic phase was separated, dried and concentrated under reduced pressure to yield 5.15 g (91% of theory) of (4-fluoro-2-methoxy-phenyl)-methanol as a white solid; MS: 156 (M)+. the mixture stirred for 30 minutes at room temperature Thereupon, most of the methanol was evaporated under reduced pressure the residue extracted with dichloromethane The organic phase was separated dried concentrated under reduced pressure

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

Procedure: An ice-cold solution of 5.6 g of 4-fluoro-2-methoxy-benzaldehyde in 75 ml of methanol was treated portionwise (5 portions within 50 minutes) with 1.51 g (40 mmol) of sodium borohydride and the reaction mixture was stirred for another 1 hour at room temperature. A dispersion of 7 g of potassium hydrogencarbonate in 20 ml of water was added and the mixture stirred for 30 minutes at room temperature. Thereupon, most of the methanol was evaporated under reduced pressure and the residue extracted with dichloromethane. The organic phase was separated, dried and concentrated under reduced pressure to yield 5.15 g (91% of theory) of (4-fluoro-2-methoxy-phenyl)-methanol as a white solid; MS: 156 (M)+. the mixture stirred for 30 minutes at room temperature Thereupon, most of the methanol was evaporated under reduced pressure the residue extracted with dichloromethane The organic phase was separated dried concentrated under reduced pressure

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

Procedure: Triethylamine (0.84 ml, 6.03 mmol) was added to a solution of 4-fluoro-2-methoxybenzylalcohol (310.8 mg, 1.99 mmol) in DMSO (7 ml). Pyridine sulfur trioxide (938.6 mg, 5.90 mmol) was added portionwise to the mixture checking raise of the temperature. The mixture was stirred for 1 hour. The mixture was added to 5% KHSO4 aqueous solution, extracted three times with ethyl acetate and dried over MgSO4. The mixture was concentrated and purified by silica gel chromatography (hexane/ether=5/1) to give the title compound (293.3 mg; 96%). checking raise of the temperature extracted three times with ethyl acetate dried over MgSO4 The mixture was concentrated purified by silica gel chromatography (hexane/ether=5/1)

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

Procedure: Triethylamine (0.84 ml, 6.03 mmol) was added to a solution of 4-fluoro-2-methoxybenzylalcohol (310.8 mg, 1.99 mmol) in DMSO (7 ml). Pyridine sulfur trioxide (938.6 mg, 5.90 mmol) was added portionwise to the mixture checking raise of the temperature. The mixture was stirred for 1 hour. The mixture was added to 5% KHSO4 aqueous solution, extracted three times with ethyl acetate and dried over MgSO4. The mixture was concentrated and purified by silica gel chromatography (hexane/ether=5/1) to give the title compound (293.3 mg; 96%). checking raise of the temperature extracted three times with ethyl acetate dried over MgSO4 The mixture was concentrated purified by silica gel chromatography (hexane/ether=5/1)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methoxide solution (25% by weight in methanol, 22.25 mL) and methanol (52 mL) were added to a flask and cooled to −20° C. using an acetonitrile/dry ice bath. Ethyl 2-azidoacetate (25% by weight in ethanol, 50.3 g) and 4-fluoro-2-methoxybenzaldehyde (5.00 g, dissolved in ethyl 2-azidoacetate solution) were added drop-wise to the stirring sodium methoxide solution at −20° C. The solution was then stirred at −20° C. for 3.5 hours, then at 0° C. for one hour. The solution was poured over ice, vacuum filtered, and washed with water. The filtered solid was taken up in xylenes (100 mL), washed twice with brine, and dried using anhydrous sodium sulfate and filtered. In a separate flask xylenes (50 mL) was brought to reflux. The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes. The solution was then refluxed for five hours, cooled, and placed in a freezer for 16 hours. The precipitate was filtered out. The volume of the filtrate was reduced on vacuum to generate a second crop of precipitate, which was washed with hexanes, then 5% ethyl acetate in hexanes and combined with material from the first filtration. at 0° C. for one hour The solution was poured over ice, vacuum filtered washed with water washed twice with brine dried filtered In a separate flask xylenes (50 mL) was brought to reflux The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes The solution was then refluxed for five hours cooled placed in a freezer for 16 hours The precipitate was filtered out was washed with hexanes 5% ethyl acetate in hexanes and combined with material from the first filtration

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methoxide solution (25% by weight in methanol, 22.25 mL) and methanol (52 mL) were added to a flask and cooled to −20° C. using an acetonitrile/dry ice bath. Ethyl 2-azidoacetate (25% by weight in ethanol, 50.3 g) and 4-fluoro-2-methoxybenzaldehyde (5.00 g, dissolved in ethyl 2-azidoacetate solution) were added drop-wise to the stirring sodium methoxide solution at −20° C. The solution was then stirred at −20° C. for 3.5 hours, then at 0° C. for one hour. The solution was poured over ice, vacuum filtered, and washed with water. The filtered solid was taken up in xylenes (100 mL), washed twice with brine, and dried using anhydrous sodium sulfate and filtered. In a separate flask xylenes (50 mL) was brought to reflux. The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes. The solution was then refluxed for five hours, cooled, and placed in a freezer for 16 hours. The precipitate was filtered out. The volume of the filtrate was reduced on vacuum to generate a second crop of precipitate, which was washed with hexanes, then 5% ethyl acetate in hexanes and combined with material from the first filtration. at 0° C. for one hour The solution was poured over ice, vacuum filtered washed with water washed twice with brine dried filtered In a separate flask xylenes (50 mL) was brought to reflux The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes The solution was then refluxed for five hours cooled placed in a freezer for 16 hours The precipitate was filtered out was washed with hexanes 5% ethyl acetate in hexanes and combined with material from the first filtration

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methoxide solution (25% by weight in methanol, 22.25 mL) and methanol (52 mL) were added to a flask and cooled to −20° C. using an acetonitrile/dry ice bath. Ethyl 2-azidoacetate (25% by weight in ethanol, 50.3 g) and 4-fluoro-2-methoxybenzaldehyde (5.00 g, dissolved in ethyl 2-azidoacetate solution) were added drop-wise to the stirring sodium methoxide solution at −20° C. The solution was then stirred at −20° C. for 3.5 hours, then at 0° C. for one hour. The solution was poured over ice, vacuum filtered, and washed with water. The filtered solid was taken up in xylenes (100 mL), washed twice with brine, and dried using anhydrous sodium sulfate and filtered. In a separate flask xylenes (50 mL) was brought to reflux. The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes. The solution was then refluxed for five hours, cooled, and placed in a freezer for 16 hours. The precipitate was filtered out. The volume of the filtrate was reduced on vacuum to generate a second crop of precipitate, which was washed with hexanes, then 5% ethyl acetate in hexanes and combined with material from the first filtration. at 0° C. for one hour The solution was poured over ice, vacuum filtered washed with water washed twice with brine dried filtered In a separate flask xylenes (50 mL) was brought to reflux The xylene solution containing the filtered material was added drop-wise to the refluxing xylenes The solution was then refluxed for five hours cooled placed in a freezer for 16 hours The precipitate was filtered out was washed with hexanes 5% ethyl acetate in hexanes and combined with material from the first filtration