8-氟-2,3-二氢苯并吡喃-4-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A round bottom flask was charged with 8-fluorochroman-4-one (8.2 g), hydroxylamine hydrochloride (3.78 g) and sodium acetate (4.46 g). A reflux condenser was added, the flask was purged with argon, dry EtOH (20 mL) was added, and the mixture was stirred at reflux for 18 hours. The solution was cooled to room temperature, diluted with EtOAc, and washed with water. The organic phase was dried, and evaporated to give the intermediate 8-fluorochroman-4-one oxime, which was reduced with Raney Nickel in EtOH at 50 PSI to yield the titled amine (4.69 g, 57%). A reflux condenser was added the flask was purged with argon, dry EtOH (20 mL) was added at reflux for 18 hours diluted with EtOAc washed with water The organic phase was dried evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Oxalyl chloride (8.79 mL) and 1 drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in DCM (50 mL). The solution was stirred at 0° C. for 2 hours, then aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with DCM. The combined organics were washed with 0.5M NaOH and brine, then dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give of the title compound (8.20 g, 98%). the solution was stirred for 16 hours at room temperature The mixture was poured onto ice water extracted three times with DCM The combined organics were washed with 0.5M NaOH and brine dried evaporated purified by column chromatography (eluting with 20% EtOAc/Hex)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Oxalyl chloride (8.79 mL) and 1 drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in DCM (50 mL). The solution was stirred at 0° C. for 2 hours, then aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with DCM. The combined organics were washed with 0.5M NaOH and brine, then dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give of the title compound (8.20 g, 98%). the solution was stirred for 16 hours at room temperature The mixture was poured onto ice water extracted three times with DCM The combined organics were washed with 0.5M NaOH and brine dried evaporated purified by column chromatography (eluting with 20% EtOAc/Hex)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A round bottom flask was charged with 8-fluorochroman-4-one (8.2 g), hydroxylamine hydrochloride (3.78 g) and sodium acetate (4.46 g). A reflux condenser was added, the flask was purged with argon, dry EtOH (20 mL) was added, and the mixture was stirred at reflux for 18 hours. The solution was cooled to room temperature, diluted with EtOAc, and washed with water. The organic phase was dried, and evaporated to give the intermediate 8-fluorochroman-4-one oxime (4), which was reduced with Raney Nickel in EtOH at 50 PSI to yield the title amine (5) (4.69 g, 57%). A reflux condenser was added the flask was purged with argon, dry EtOH (20 mL) was added at reflux for 18 hours diluted with EtOAc washed with water The organic phase was dried evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A round bottom flask was charged with 8-fluorochroman-4-one (8.2 g), hydroxylamine hydrochloride (3.78 g) and sodium acetate (4.46 g). A reflux condenser was added, the flask was purged with argon, dry EtOH (20 mL) was added, and the mixture was stirred at reflux for 18 hours. The solution was cooled to room temperature, diluted with EtOAc, and washed with water. The organic phase was dried, and evaporated to give the intermediate 8-fluorochroman-4-one oxime (4), which was reduced with Raney Nickel in EtOH at 50 PSI to yield the title amine (5) (4.69 g, 57%). A reflux condenser was added the flask was purged with argon, dry EtOH (20 mL) was added at reflux for 18 hours diluted with EtOAc washed with water The organic phase was dried evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Oxalyl chloride (8.79 mL) and one drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in methylene chloride (50 mL). The solution was stirred at 0° C. for two hours, aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with methylene chloride. The combined organics were washed with 0.5M NaOH and brine, dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give 8-fluorochroman-4-one (3) (8.20 g, 98%). the solution was stirred for 16 hours at room temperature The mixture was poured onto ice water extracted three times with methylene chloride The combined organics were washed with 0.5M NaOH and brine dried evaporated purified by column chromatography (eluting with 20% EtOAc/Hex)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A round bottom flask was charged with 8-fluorochroman-4-one (8.2 g), hydroxylamine hydrochloride (3.78 g) and sodium acetate (4.46 g). A reflux condenser was added, the flask was purged with argon, dry EtOH (20 mL) was added, and the mixture was stirred at reflux for 18 hours. The solution was cooled to room temperature, diluted with EtOAc, and washed with water. The organic phase was dried, and evaporated to give the intermediate 8-fluorochroman-4-one oxime (4), which was reduced with Raney Nickel in EtOH at 50 PSI to yield the title amine (5) (4.69 g, 57%). A reflux condenser was added the flask was purged with argon, dry EtOH (20 mL) was added at reflux for 18 hours diluted with EtOAc washed with water The organic phase was dried evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Oxalyl chloride (8.79 mL) and one drop of DMF were added to an ice cold solution of 3-(2-fluorophenoxy)propanoic acid (9.27 g) in methylene chloride (50 mL). The solution was stirred at 0° C. for two hours, aluminum chloride (7.39 g, 55.42 mM) was added and the solution was stirred for 16 hours at room temperature. The mixture was poured onto ice water, and extracted three times with methylene chloride. The combined organics were washed with 0.5M NaOH and brine, dried, evaporated, and purified by column chromatography (eluting with 20% EtOAc/Hex) to give 8-fluorochroman-4-one (3) (8.20 g, 98%). the solution was stirred for 16 hours at room temperature The mixture was poured onto ice water extracted three times with methylene chloride The combined organics were washed with 0.5M NaOH and brine dried evaporated purified by column chromatography (eluting with 20% EtOAc/Hex)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Potassium t-butoxide (2.42 g) was added to a solution of the compound 1-1 (2.20 g) in tetrahydrofuran (100 ml) at room temperature. After stirring for five minutes at the same temperature, beta-propiolactone (2.71 ml) was added. Because of heat generation, the mixture was moved to an ice bath and stirred at the same temperature for one hour. After further stirring at room temperature for four hours, the mixture was made acidic with 1 N hydrochloric acid to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized by adding a mixed solvent of 20% ethyl acetate-hexane to obtain the title compound (1.44 g). was added Because of heat generation, the mixture was moved to an ice bath After further stirring at room temperature for four hours to terminate the reaction The aqueous layer was extracted with ethyl acetate the organic layer was washed with brine The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was crystallized by adding a mixed solvent of 20% ethyl acetate-hexane