2-methyl-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:

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

Procedure: To a cooled solution (−70° C.) of LDA (1 M) in THF (37 mL) was added dropwise a solution of 2-methyl-1-indanone (J.A.C.S. Vol. 98, 8119-8124 (1976)) (2.5 g, 17 mmol) in THF (20 mL). The resulting dark red solution was stirred at room temperature for 3 hours, then cooled to −20° C. and a solution for 4-methylthiobenzyl chloride (3.1 g, 18 mmol) in THF (15 mL) was added slowly. The addition completed, the reaction mixture was stirred at −20° C. for 30 minutes before being quenched with 3N aqueous HCl (50 mL) and brine (50 mL). The product was extracted with ether, dried over MgSO4 and evaporated to dryness. The oily residue was chromatographed on silica gel eluting with a 1:5 mixture of ethyl acetate-hexane to afford the pure title compound as an oil. cooled to −20° C. The addition the reaction mixture was stirred at −20° C. for 30 minutes before being quenched with 3N aqueous HCl (50 mL) and brine (50 mL) The product was extracted with ether dried over MgSO4 evaporated to dryness The oily residue was chromatographed on silica gel eluting with a 1:5 mixture of ethyl acetate-hexane

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

Procedure: A 200 ml four-necked flask equipped with a reflux tube, a thermometer and a dropping funnel was thoroughly purged with nitrogen and dried. To the flask, methylmagnesium bromide (3.0 mol/l ether solution) (16.9 ml, 50.7 mmol) and dehydrated ether (50 ml) were introduced. To the flask, a solution of 2-methyl-1-indanon (3.70 g, 25.3 mmol) in dehydrate ether (20 ml) was dropwise added at room temperature with stirring. Then, the reaction mixture was stirred for 2 hours and poured into cold water. The resultant mixture was introduced into a separatory funnel to separate an organic phase. The aqueous phase was extracted by ether (100 ml×3) and a combined organic phase was washed with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 1,2-dimethyl-1-hydroxy-indene. The compound thus obtained was dissolved in toluene (30 ml) and, thereto, 0.1 g of p-toluenesulphonic acid was added. The reaction mixture was refluxed for 3 hours to remove water. The organic phase thus obtained was introduced into a separatory funnel and washed with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After removing a solvent, it was purified by column chromatography (developer; hexane) to obtain 2.70 g (GC 94%) of a pale yellow solution (yield: 74%). A 200 ml four-necked flask equipped with a reflux tube a thermometer and a dropping funnel was thoroughly purged with nitrogen dried Then, the reaction mixture was stirred for 2 hours to separate an organic phase The aqueous phase was extracted by ether (100 ml×3) a combined organic phase was washed with a saturated aqueous solution of ammonium chloride, water a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate The solvent was distilled off

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

Procedure: Analogously to Example D, 5.0 g (34 mmol) of 2-methyl-1-indanone (5) were reduced with 1.94 g (51 mmol) of NaBH4. The alcohol, which was not purified further, was then further reacted in the presence of 0.2 g of p-toluene-sulfonic acid in 100 ml of toluene at 80° C. Chromatography on 100 g of silica gel (hexane/methylene chloride 9:1) gave 3.68 g (82%) of 2-methylindene (6). The alcohol, which was not purified further was then further reacted in the presence of 0.2 g of p-toluene-sulfonic acid in 100 ml of toluene at 80° C

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

Procedure: 17.3 g (125 mmol) of AlCl3 were added to a solution of 3.91 g (50 mmol) of benzene in 30 ml of analytical grade methylene chloride, while cooling with ice. 11.9 g (52 mmol) of 2-bromoisobutyryl bromide were then added, and stirring was continued at 0° C. for 1 hour and at room temperature for 2 hours. The mixture was heated under reflux for a further 15 hours and then worked up analogously to Example A. The crude product was chromatographed on 100 g of silica gel (hexane/methylene chloride 1:1). The yield was 5.1 g (70%). while cooling with ice The mixture was heated under reflux for a further 15 hours The crude product was chromatographed on 100 g of silica gel (hexane/methylene chloride 1:1)

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to the procedure of Farnum et. al (Synthesis 1972, 191-192.), water (1.35 L) is stirred at 80° C. and de-gassed by periodic evacuating and flushing with nitrogen (3×). K3FeCN6 (202 g, 615 mmol) and 2-methyl-indan-1-one (20 g, 137 mmol) are added. The mixture is stirred rapidly under nitrogen at 80° C. while aqueous concentrated ammonia solution (105 mL) is added over 30 minutes. Stirring is continued at 80° C. for 20 hours. When cool, the solution is made alkaline by addition of sodium hydroxide (2 g) and extracted with ethyl acetate (2×200 mL). The organic extract is concentrated to a volume of 200 ml and the product is extracted into aqueous HCl (200 mL, 1M). The acidic aqueous phase is separated, basified with sodium hydroxide, and extracted with ethyl acetate (2×100 mL). The organic layer is separated, dried (Na2SO4) and the solvent removed to give an orange oil. de-gassed by periodic evacuating flushing with nitrogen (3×) is added over 30 minutes Stirring When cool extracted with ethyl acetate (2×200 mL) The organic extract is concentrated to a volume of 200 ml the product is extracted into aqueous HCl (200 mL, 1M) The acidic aqueous phase is separated extracted with ethyl acetate (2×100 mL) The organic layer is separated dried (Na2SO4) the solvent removed to give an orange oil

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to the procedure of Farnum et. al (Synthesis 1972, 191-192.), water (1.35 L) is stirred at 80° C. and de-gassed by periodic evacuating and flushing with nitrogen (3×). K3FeCN6 (202 g, 615 mmol) and 2-methyl-indan-1-one (20 g, 137 mmol) are added. The mixture is stirred rapidly under nitrogen at 80° C. while aqueous concentrated ammonia solution (105 mL) is added over 30 minutes. Stirring is continued at 80° C. for 20 hours. When cool, the solution is made alkaline by addition of sodium hydroxide (2 g) and extracted with ethyl acetate (2×200 mL). The organic extract is concentrated to a volume of 200 ml and the product is extracted into aqueous HCl (200 mL, 1M). The acidic aqueous phase is separated, basified with sodium hydroxide, and extracted with ethyl acetate (2×100 mL). The organic layer is separated, dried (Na2SO4) and the solvent removed to give an orange oil. de-gassed by periodic evacuating flushing with nitrogen (3×) is added over 30 minutes Stirring When cool extracted with ethyl acetate (2×200 mL) The organic extract is concentrated to a volume of 200 ml the product is extracted into aqueous HCl (200 mL, 1M) The acidic aqueous phase is separated extracted with ethyl acetate (2×100 mL) The organic layer is separated dried (Na2SO4) the solvent removed to give an orange oil

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.70 ml of n-BuLi (16.8 mmol) were added dropwise at 100° C. to 3.50 g of o-bromoquinoline (16.8 mmol) dissolved in 50 ml of THF, and the mixture was subsequently stirred at 80° C. for 15 minutes. A solution of 50 ml of THF and 2.45 g of 2-methyl-1-indanone (16.8 mmol) was then added to the lithiated bromoquinoline over the course of 10 minutes. The mixture was allowed to cool to room temperature, and the solution was then refluxed for three hours, cooled to room temperature, acidified to pH 1 using ice and hydrochloric acid and subsequently refluxed for three hours. The reaction mixture was adjusted to pH 9 using ammonia solution, and the aqueous phase was extracted with diethyl ether. The combined organic phases were dried, and the solvent was removed. The crude product was purified by distillation under reduced pressure at 150-160° C./10−2 mbar, giving 1.5 g of 1-(8-quinolyl)-2-methylindene (45%) as a yellow, viscous resin. to cool to room temperature the solution was then refluxed for three hours cooled to room temperature subsequently refluxed for three hours the aqueous phase was extracted with diethyl ether The combined organic phases were dried the solvent was removed The crude product was purified by distillation under reduced pressure at 150-160° C./10−2 mbar

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

Procedure: Analogously to Example D, 5.0 g (34 mmol) of 2-methyl-1-indanone (5) were reduced with 1.94 g (51 mmol) of NaBH4. The alcohol, which was not purified further, was then further reacted in the presence of 0.2 g of p-toluenesulfonic acid in 100 ml of toluene at 80° C. Chromatography on 100 g of silica gel (hexane/methylene chloride 9:1) gave 3.68 g (82%) of 2-methylindene (6). The alcohol, which was not purified further was then further reacted in the presence of 0.2 g of p-toluenesulfonic acid in 100 ml of toluene at 80° C