5-fluoro-3,4-dihydro-2H-naphthalen-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: To the 4-(2-fluorophenyl)butyryl chloride in carbon disulfide (1.0 L) at -78° C. was added aluminum chloride (93.2 g, 0.7 mol) portionwise over a 30 min period. The mixture was warmed to room temperature for 30 min, then refluxed for 2 h. The reaction mixture was poured into a mixture of ice (500 mL) and HCl (6N, 500 mL). The carbon disulfide layer was separated, washed with saturated sodium bicarbonate and extracted with ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined extracts were dried (MgSO4) and concentrated in vacuo to give 84.2 g (93%) of 5-fluorotetralone as a tan solid. NMR (CDCl3): d 7.7 (m, 1H, ArH), 7.1 (m, 2H, ArH), 2.9 (t, 2H, CH2), 2.6 (t, 2H, CH2), 2.1 (q, 2H, CH2). refluxed for 2 h The carbon disulfide layer was separated washed with saturated sodium bicarbonate extracted with ethyl acetate The aqueous phase was extracted with ethyl acetate The combined extracts were dried (MgSO4) concentrated in vacuo

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

実験手順: 14 gm of the compound prepared in (7) above was dissolved into 100 ml of concentrated sulfuric acid. After cooling the solution, a solution of 9.05 gm of potassium nitrate in 80 ml of concentrated sulfuric acid was added dropwise while maintaining the internal temperature below 5° C. The stirring was continued for a further 30 minutes. The resultant reaction mixture was poured into ice-cooled water and extracted with chloroform. The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated and residue was recrystallized in methanol to obtain 9.15 gm of the title compound. After cooling the solution while maintaining the internal temperature below 5° C The resultant reaction mixture was poured into ice- extracted with chloroform The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order dried over anhydrous sodium sulfate The solvent was evaporated residue was recrystallized in methanol

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

実験手順: To 200 gm of polyphosphoric acid heated at 80° C. was added 15.9 gm of the compound prepared in (6) above over 1 hour while stirring. The stirring was continued for another 1 hour at the same temperature. The resultant reaction mixture was poured into ice-cooled water and extracted with chloroform. The extract was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain 14.1 gm of the title compound. The resultant reaction mixture was poured into ice- extracted with chloroform The extract was washed with water and saturated brine in this order dried over anhydrous sodium sulfate The solvent was evaporated

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

実験手順: To a suspension of 60% sodium hydride (5.00 g) in toluene (250 ml) was added dropwise ethyl diethylphosphonoacetate (23.9 ml) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Then, a solution of 5-fluoro-3,4-dihydro-2H-naphthalen-1-one (18.0 g) in toluene (50 ml) was added dropwise, and the mixture was stirred at 80° C. for 3 hr. After cooling to room temperature, the reaction mixture was poured into ice water, and the mixture was extracted with toluene. The extract was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give ethyl (5-fluoro-3,4-dihydronaphthalen-1-yl)acetate (17.4 g). cooling the mixture was stirred at 80° C. for 3 hr After cooling to room temperature the mixture was extracted with toluene The extract was washed with water and saturated brine dried over magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

実験手順: To a suspension of 60% sodium hydride (4.12 g) in toluene (200 ml) was added dropwise ethyl diethylphosphonoacetate (20.4 ml) under ice-cooling, and the mixture was stirred at room temperature for 45 min. Then, a solution of 5-fluoro-3,4-dihydro-2H-naphthalen-1-one (15.3 g) in toluene (50 ml) was added dropwise, and the mixture was stirred at 80° C. for 2 hr. After cooling to room temperature, the reaction mixture was poured into ice water, and the mixture was extracted with toluene. The extract was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give ethyl (5-fluoro-3,4-dihydro-2H-naphthalen-1-ylidene)acetate. cooling the mixture was stirred at 80° C. for 2 hr After cooling to room temperature the mixture was extracted with toluene The extract was washed with water and saturated brine dried over magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

実験手順: 14 gm of the compound prepared in (7) above was dissolved into 100 ml of concentrated sulfuric acid. After cooling the solution, a solution of 9.05 gm of potassium nitrate in 80 ml of concentrated sulfuric acid was added dropwise while maintaining the internal temperature below 5° C. The stirring was continued for a further 30 minutes. The resultant reaction mixture was poured into ice-cooled water and extracted with chloroform. The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated and residue was recrystallized in methanol to obtain 9.15 gm of the title compound. After cooling the solution while maintaining the internal temperature below 5° C The resultant reaction mixture was poured into ice- extracted with chloroform The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order dried over anhydrous sodium sulfate The solvent was evaporated residue was recrystallized in methanol

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

実験手順: 14 gm of the compound prepared in (7) above was dissolved into 100 ml of concentrated sulfuric acid. After cooling the solution, a solution of 9.05 gm of potassium nitrate in 80 ml of concentrated sulfuric acid was added dropwise while maintaining the internal temperature below 5° C. The stirring was continued for a further 30 minutes. The resultant reaction mixture was poured into ice-cooled water and extracted with chloroform. The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated and residue was recrystallized in methanol to obtain 9.15 gm of the title compound. After cooling the solution while maintaining the internal temperature below 5° C The resultant reaction mixture was poured into ice- extracted with chloroform The extract was washed with saturated aqueous solution of sodium bicarbonate, water, and saturated brine in this order dried over anhydrous sodium sulfate The solvent was evaporated residue was recrystallized in methanol

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

実験手順: To 200 gm of polyphosphoric acid heated at 80° C. was added 15.9 gm of the compound prepared in (6) above over 1 hour while stirring. The stirring was continued for another 1 hour at the same temperature. The resultant reaction mixture was poured into ice-cooled water and extracted with chloroform. The extract was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain 14.1 gm of the title compound. The resultant reaction mixture was poured into ice- extracted with chloroform The extract was washed with water and saturated brine in this order dried over anhydrous sodium sulfate The solvent was evaporated

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

実験手順: A solution of 5-fluoro-3,4-dihydronaphthalen-1(2H)-one (1.26 mmol) in MeOH (4 mL) at 0° C. was quickly charged with a solution of sodium borohydride (3.23 mmol, 2.5 eq) in MeOH (2 mL). The reaction was stirred for 1.5 h from 0° C. to ambient temperature. The reaction was quenched with water and extracted with ether. All organic layers were combined and dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was dissolved in minimal CH2Cl2 and was purified by chromatography on silica gel [0.5″×10″ glass column, eluting with neat CH2Cl2→5:1 CH2Cl2:EtOAc]. Fractions containing product were combined and concentrated in vacuo, giving the title material as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ=1.73 (d, J=6.8 Hz, 1H), 1.75-1.90 (m, 2H), 1.91-2.10 (m, 2H), 2.61-2.86 (m, 2H), 4.67-4.83 (m, 1H), 6.90 (ddd, J=8.5, 8.5, 2.8 Hz, 1H), 7.06 (dd, J=8.5, 5.7 Hz, 1H), 7.17 (dd, J=9.6, 2.8 Hz, 1H). MS (ES+): m/z 149.02 (100) [MH+−OH]. HPLC: tR=2.96 min (ZQ3, polar—5 min). The reaction was quenched with water extracted with ether dried over anhydrous Na2SO4 filtered concentrated in vacuo The crude was dissolved in minimal CH2Cl2 was purified by chromatography on silica gel [0.5″×10″ glass column eluting with neat CH2Cl2→5:1 CH2Cl2 Fractions containing product concentrated in vacuo