5-fluoro-2-hydroxybenzamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

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

実験手順: 4.3 g of 5-fluoro-salicylamide and 4.7 g of 5-fluorosalicylic acid are boiled under reflux in 50 ml of xylene after addition of 0.3 ml of pyridine. 4.4 ml of thionyl chloride are added in the course of 2 h, the mixture is stirred for a further 1 h and the solvent is then distilled off under reduced pressure. The residue is suspended in 30 ml of ethanol, filtered off and washed with ethanol. After drying, 6-fluoro-2-(5-fluoro-2-hydroxyphenyl)benz[e][1,3]oxazin-4-one is obtained as slightly yellow crystals of m.p. 250-252 C. the solvent is then distilled off under reduced pressure filtered off washed with ethanol After drying

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals. m.p. 90°-93° C. The reaction mixture was then heated to 100° C. for 18 hr The dimethylformamide was removed by rotary evaporation at 70° C. washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water The organic phase was extracted with 2×50 ml of 1N hydrochloric acid The combined aqueous extracts were washed with 50 ml of methylene chloride extracted into 2×50 ml of methylene chloride The combined organic extracts were dried over sodium sulfate filtered concentrated by rotary evaporation The residual oil was crystallized from hexane

反応条件: temp:0.00; pressure:0.00; stir: