6-fluoro-2,3-dihydroinden-1-one

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

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

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

Procedure: A mixture of N-bromosuccinimide (2.76 g, 15.51 mmoles, Aldrich), benzoyl peroxide (0.01 g, 0.04 mmoles, Aldrich) and 6fluoro-1-indanone (2.29 g, 15.25 mmoles) in carbon tetrachloride (20 mL) was refluxed under nitrogen for two hours. The mixture was cooled to ambient temperature, filtered, and the solids were washed with dichloromethane. The washings and filtrate were combined, washed successively with 1.0N sodium hydroxide (2×30 mL), water (2×30 mL) and brine (30 mL), and evaporated in vacuo. The residue was chromatographed on silica gel eluting first with hexane, gradually increasing the polarity to hexane: ethyl acetate (95:5). The fractions containing the major spot were combined and evaporated in vacuo to give a 2.30 g (66%) of 3-bromo-6-fluoro-1-indanone as a yellow oil which was used without further purification. was refluxed under nitrogen for two hours filtered the solids were washed with dichloromethane washed successively with 1.0N sodium hydroxide (2×30 mL), water (2×30 mL) and brine (30 mL) evaporated in vacuo The residue was chromatographed on silica gel eluting first with hexane gradually increasing the polarity to hexane: ethyl acetate (95:5) The fractions containing the major spot evaporated in vacuo

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

Procedure: A mixture of 6-fluoro-1-indanone (5.0 g, 33.3 mmol), ethyl bromoacetate (8.3 g, 50.0 mmol, Aldrich), activated zinc powder (3.2 g, 50.0 mmol, Mallinckrodt; Org. Synth., Coll. Vol. 6, 290, 1988) and a few crystals of iodine in diethyl ether-benzene (1:1, 100 mL) was heated at reflux under nitrogen for 24 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue in diethyl ether was vigorously stirred with excess dilute ammonium hydroxide, dried and concentrated to give ethyl 2-(6-fluoro-1-hydroxy-1-indanyl)acetate as an amber oil (7.6 g, 97%); at reflux under nitrogen for 24 h The mixture was filtered the filtrate was concentrated in vacuo dried concentrated

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

Procedure: A solution of 3-(4-fluorophenyl)propionyl chloride (287.6 g, 1.5 mol) in dichloromethane (1.4 L) was added dropwise during 3 h to an ice-cold, mechanically stirred suspension of aluminum chloride (226.0 g, 1.7 mol, Aldrich) in dichloromethane (2.2 L) under nitrogen. The resulting yellowish-black solution was refluxed for 5 h and allowed to cool to room temperature. The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to a tan solid (229.1 g, 99%). The solid was recrystallized from dichloromethane-hexane to give 215.7 g (93%) of 6-fluoro-1-indanone as off-white crystals, m.p., 57°-59° C.; The resulting yellowish-black solution was refluxed for 5 h The solution was washed successively with water (2 L), 1N sodium hydroxide (2 L), water (2 L) and brine (2 L) The organic layer was dried over anhydrous sodium sulfate filtered concentrated to a tan solid (229.1 g, 99%) The solid was recrystallized from dichloromethane-hexane

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

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

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

Procedure: A solution of 19.7 g of 6-fluoro-1-indanone, 27.0 ml of 3-buten-2-ol and 200 mg of p-toluenesulfonic acid in 200 ml of 2,2-dimethoxypropane was boiled under reflux for 67 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). 18.9 g (71%) of (RS)-2-(2-buten-1-yl)-6-fluoro-1-indanone were obtained as a yellow oil. separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped) The reaction mixture was subsequently concentrated in a vacuum purified by column chromatography on silica gel (hexane/diethyl ether 4:1)

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

Procedure: A solution of 19.7 g of 6-fluoro-1-indanone, 27.0 ml of 3-buten-2-ol and 200 mg of p-toluenesulfonic acid in 200 ml of 2,2-dimethoxypropane was boiled under reflux for 67 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). 18.9 g (71%) of (RS)-2-(2-buten-1-yl)-6-fluoro-1-indanone were obtained as a yellow oil. separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped) The reaction mixture was subsequently concentrated in a vacuum purified by column chromatography on silica gel (hexane/diethyl ether 4:1)

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

Procedure: To a solution of 6-fluoro-indan-1-one (0.50 g, 3.3 mmol) in DCE (10 mL) and MeOH (10 mL) was added NaBH4 (0.25 g, 6.6 mmol). After 30 min the reaction was quenched with H2O (10 mL) and extracted with CH2Cl2 (3×20 mL). The organic layers were combined and dried to give the title compound (0.49 g, 97%). MS (ESI): mass calcd. for C9H7FO, 150.1; m/z found, 151.4 [M+H]+. 1H NMR (CDCl3): 7.23-7.13 (m, 1H), 7.09 (dd, J=8.6, 2.5 Hz, 1H), 6.99-6.90 (m, 1H), 5.21 (t, J=6.3 Hz, 1H), 3.13-2.91 (m, 1H), 2.85-2.68 (m, 1H), 2.63-2.44 (m, 1H), 2.09-1.74 (m, 2H). After 30 min the reaction was quenched with H2O (10 mL) extracted with CH2Cl2 (3×20 mL) dried

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

Procedure: To a solution of 6-fluoro-indan-1-one (0.5 g, 3.33 mmol) in pyridine (10 ml) was added the HCl salt of methoxylamine (0.31 g, 3.66 mmol) and stirred at room temperature for overnight. The reaction mixture was diluted with ethylacetate (50 ml), acidified with 3N HCl, and washed with 1N HCl, water and brine sequentially. The solution was dried (Na2SO4) and concentrated to yield 0.48 g (81%) of product. MS (ESI+) m/z 180 (M+H)+; washed with 1N HCl, water and brine sequentially The solution was dried (Na2SO4) concentrated

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

Procedure: To a solution of 6-fluoro-indan-1-one (0.5 g, 3.33 mmol) in pyridine (10 ml) was added the HCl salt of methoxylamine (0.31 g, 3.66 mmol) and stirred at room temperature for overnight. The reaction mixture was diluted with ethylacetate (50 ml), acidified with 3N HCl, and washed with 1N HCl, water and brine sequentially. The solution was dried (Na2SO4) and concentrated to yield 0.48 g (81%) of product. MS (ESI+) m/z 180 (M+H)+; washed with 1N HCl, water and brine sequentially The solution was dried (Na2SO4) concentrated