7-fluoro-2,2-dimethyl-3H-chromen-4-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 7-fluoro-2,2-dimethyl-2,3-dihydrochromen-4-one (1.000 g, 5.149 mmol) was added trimethylsilyl cyanide (3.215 mL, 25.75 mmol) followed by a spatula tip of zinc iodide. The reaction was heated at 50° C. for 1 hour. The reaction was cooled, diluted with ethyl acetate (40 mL) and washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL), dried over magnesium sulfate and concentrated. The product was dissolved in 5 mL of acetic acid and 5 mL of HCl, and SnCl2 dihydrate (4.648 g, 20.60 mmol) was added. The reaction heated at reflux (130° C. oil bath temperature) overnight. The reaction was cooled, diluted with ethyl acetate (50 mL), washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid to provide the title compound (0.280 g, 24.25% yield). The reaction was cooled washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL) dried over magnesium sulfate concentrated The product was dissolved in 5 mL of acetic acid The reaction heated at reflux (130° C. oil bath temperature) overnight The reaction was cooled washed with water (50 mL) and brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (5.75 g, 37.3 mmol) and propan-2-one (12 mL, 37.3 mmol) in benzene (50 mL) was added pyrrolidine (3.11 mL, 37.3 mmol) and the reaction heated at 80° C. for 3 hours. The reaction was diluted with ethyl acetate (50 mL), washed with 1N HCl (50 mL), brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate, to provide the title compound (5.12 g, 70.7% yield). washed with 1N HCl (50 mL), brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 7-fluoro-2,2-dimethyl-2,3-dihydrochromen-4-one (1.000 g, 5.149 mmol) was added trimethylsilyl cyanide (3.215 mL, 25.75 mmol) followed by a spatula tip of zinc iodide. The reaction was heated at 50° C. for 1 hour. The reaction was cooled, diluted with ethyl acetate (40 mL) and washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL), dried over magnesium sulfate and concentrated. The product was dissolved in 5 mL of acetic acid and 5 mL of HCl, and SnCl2 dihydrate (4.648 g, 20.60 mmol) was added. The reaction heated at reflux (130° C. oil bath temperature) overnight. The reaction was cooled, diluted with ethyl acetate (50 mL), washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid to provide the title compound (0.280 g, 24.25% yield). The reaction was cooled washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL) dried over magnesium sulfate concentrated The product was dissolved in 5 mL of acetic acid The reaction heated at reflux (130° C. oil bath temperature) overnight The reaction was cooled washed with water (50 mL) and brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (5.75 g, 37.3 mmol) and propan-2-one (12 mL, 37.3 mmol) in benzene (50 mL) was added pyrrolidine (3.11 mL, 37.3 mmol) and the reaction heated at 80° C. for 3 hours. The reaction was diluted with ethyl acetate (50 mL), washed with 1N HCl (50 mL), brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate, to provide the title compound (5.12 g, 70.7% yield). washed with 1N HCl (50 mL), brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (5.75 g, 37.3 mmol) and propan-2-one (12 mL, 37.3 mmol) in benzene (50 mL) was added pyrrolidine (3.11 mL, 37.3 mmol) and the reaction heated at 80° C. for 3 hours. The reaction was diluted with ethyl acetate (50 mL), washed with 1N HCl (50 mL), brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate, to provide the title compound (5.12 g, 70.7% yield). washed with 1N HCl (50 mL), brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 7-fluoro-2,2-dimethyl-2,3-dihydrochromen-4-one (1.000 g, 5.149 mmol) was added trimethylsilyl cyanide (3.215 mL, 25.75 mmol) followed by a spatula tip of zinc iodide. The reaction was heated at 50° C. for 1 hour. The reaction was cooled, diluted with ethyl acetate (40 mL) and washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL), dried over magnesium sulfate and concentrated. The product was dissolved in 5 mL of acetic acid and 5 mL of HCl, and SnCl2 dihydrate (4.648 g, 20.60 mmol) was added. The reaction heated at reflux (130° C. oil bath temperature) overnight. The reaction was cooled, diluted with ethyl acetate (50 mL), washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid to provide the title compound (0.280 g, 24.25% yield). The reaction was cooled washed with saturated sodium bicarbonate (2×25 mL), brine (25 mL) dried over magnesium sulfate concentrated The product was dissolved in 5 mL of acetic acid The reaction heated at reflux (130° C. oil bath temperature) overnight The reaction was cooled washed with water (50 mL) and brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography over silica gel eluting with a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% MeOH/CH2Cl2 containing 0.5% acetic acid

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (5.75 g, 37.3 mmol) and propan-2-one (12 mL, 37.3 mmol) in benzene (50 mL) was added pyrrolidine (3.11 mL, 37.3 mmol) and the reaction heated at 80° C. for 3 hours. The reaction was diluted with ethyl acetate (50 mL), washed with 1N HCl (50 mL), brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate, to provide the title compound (5.12 g, 70.7% yield). washed with 1N HCl (50 mL), brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (5.75 g, 37.3 mmol) and propan-2-one (12 mL, 37.3 mmol) in benzene (50 mL) was added pyrrolidine (3.11 mL, 37.3 mmol) and the reaction heated at 80° C. for 3 hours. The reaction was diluted with ethyl acetate (50 mL), washed with 1N HCl (50 mL), brine (50 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate, to provide the title compound (5.12 g, 70.7% yield). washed with 1N HCl (50 mL), brine (50 mL) dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate

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

実験手順: 1-(4-Fluoro-2-hydroxy-phenyl)-ethanone (5.0 g, 32.44 mmol), acetone (11.92 mL, 162.2 mmol) and pyrrolidine (2.7 mL, 32.44 mmol) were dissolved in 20 mL benzene, and the reaction mixture was refluxed for four hours. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and 1 N HCl. The organic layer was dried over MgSO4, and solvent was evaporated under reduced pressure. The resulting residue was chromatographed (15% ethyl acetate in hexanes eluting through silica) and solvent was removed to yield 3.33 g (17.16 mg, 53%) of 7-fluoro-2,2-dimethyl-chroman-4-one as an oil. MS: 195 (M+H)+. the reaction mixture was refluxed for four hours partitioned between ethyl acetate and 1 N HCl The organic layer was dried over MgSO4, and solvent was evaporated under reduced pressure The resulting residue was chromatographed (15% ethyl acetate in hexanes eluting through silica) and solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 1-(4-Fluoro-2-hydroxy-phenyl)-ethanone (5.0 g, 32.44 mmol), acetone (11.92 mL, 162.2 mmol) and pyrrolidine (2.7 mL, 32.44 mmol) were dissolved in 20 mL benzene, and the reaction mixture was refluxed for four hours. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and 1 N HCl. The organic layer was dried over MgSO4, and solvent was evaporated under reduced pressure. The resulting residue was chromatographed (15% ethyl acetate in hexanes eluting through silica) and solvent was removed to yield 3.33 g (17.16 mg, 53%) of 7-fluoro-2,2-dimethyl-chroman-4-one as an oil. MS: 195 (M+H)+. the reaction mixture was refluxed for four hours partitioned between ethyl acetate and 1 N HCl The organic layer was dried over MgSO4, and solvent was evaporated under reduced pressure The resulting residue was chromatographed (15% ethyl acetate in hexanes eluting through silica) and solvent was removed