6-Fluoro-2-methylindanone

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:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g polyphosphoric acid at 70° C. (steam bath) is added p-fluoro-α-methylhydrocinnamic acid (93.2 g, 0.5 mol) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at this temperature for 1 hour. The mixture is allowed to cool and is added to 2 l. of water. The aqueous suspension is extracted with ether. The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water, and is dried, and is concentrated on 200 g silica-gel; the slurry is added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether, to give 6-fluoro-2-methylindanone. Elution is followed by TLC. to cool is added to 2 l The aqueous suspension is extracted with ether The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water is dried is concentrated on 200 g silica-gel the slurry is added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

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

実験手順: A mixture of 6-fluoro-2-methylindanone (18.4 g, 0.112 mol), cyanoacetic acid (10.5 g, 0.123 mol), acetic acid (6.6 g), and ammonium acetate (1.7 g) in dry toluene (15.5 ml) is refluxed for 21 hours, as the liberated water is collected in a Dean Stark trap. The mixture is evaporated to dryness, and the residue is dissolved in hot ethanol (60 ml) and 2.2 N aqueous potassium hydroxide solution (14 ml). 85% KOH (22 g) in water (150 ml) is added, and the mixture is refluxed for 13 hours under nitrogen. The ethanol is removed in vacuo, and water (500 ml) is added. The aqueous solution is washed well with ether and is boiled with charcoal, and is filtered. The aqueous filtrate is acidified to pH 2 with 50% cold hydrochloric acid. The precipitate yields the title compound, 5-fluoro-2-methylinden-3-yl acetic acid (m.p. 164-166° C.). is collected in a Dean Stark trap The mixture is evaporated to dryness the residue is dissolved in hot ethanol (60 ml) 85% KOH (22 g) in water (150 ml) is added the mixture is refluxed for 13 hours under nitrogen The ethanol is removed in vacuo, and water (500 ml) is added The aqueous solution is washed well with ether is filtered

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To polyphosphoric acid (932 g) at 70° C. on the steam bath is added p-fluoro-α-methylhydrocinnamic acid (93.2 g, 0.5 mole) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at that temperature for 1 hour. The mixture is allowed to cool and added to 2 liters of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 g silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. to cool The aqueous layer is extracted with ether the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water dried The ether filtrate is concentrated with 200 g silica-gel added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g. polyphosphoric acid at 70° on the steam bath is added ρ-fluoro-a-methylhydrocinnamic acid (93.2 g., 0.5 mole) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture kept at this temperature for 1 hour. The mixture is allowed to cool and added to 2 l. of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 g. silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. to cool added to 2 l The aqueous layer is extracted with ether the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water dried The ether filtrate is concentrated with 200 g silica-gel, and added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g. polyphosphoric acid at 70° on the steam bath is added ρ-fluoro-a-methylhydrocinnamic acid (93.2 g., 0.5 mole) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture kept at this temperature for 1 hour. The mixture is allowed to cool and added to 2 l. of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 g. silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. to cool added to 2 l The aqueous layer is extracted with ether the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water dried The ether filtrate is concentrated with 200 g silica-gel, and added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g polyphosphoric acid at 70° C. (steam bath) is added p-fluoro-α-methylhydrocinnamic acid (93.2 g, 0.5 mol) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at this temperature for 1 hour. The mixture is allowed to cool and is added to 2 l. of water. The aqueous suspension is extracted with ether. The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water, and is dried, and is concentrated on 200 g silica-gel; the slurry is added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether, to give 6-fluoro-2-methylindanone. Elution is followed by TLC. to cool is added to 2 l The aqueous suspension is extracted with ether The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water is dried is concentrated on 200 g silica-gel the slurry is added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g polyphosphoric acid at 70° C. (steam bath) is added p-fluoro-α-methylhydrocinnamic acid (93.2 g, 0.5 mol) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at this temperature for 1 hour. The mixture is allowed to cool and is added to 2 l. of water. The aqueous suspension is extracted with ether. The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water, and is dried, and is concentrated on 200 g silica-gel; the slurry is added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether, to give 6-fluoro-2-methylindanone. Elution is followed by TLC. to cool is added to 2 l The aqueous suspension is extracted with ether The extract is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, and water is dried is concentrated on 200 g silica-gel the slurry is added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 932 g polyphosphoric acid at 70° C. (on the steam bath) is added p-fluoro-α-methylhydrocinnamic acid (93.2 g, 0.5 mol) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at this temperature for 1 hour. The mixture is allowed to cool and added to 2l. of water. The aqueous layer is extracted with ether, the ether solution is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and is then dried. The ether filtrate is concentrated with 200 g silica-gel, and is added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether, to give 6-fluoro-2-methylindanone. Elution is followed by TLC. to cool The aqueous layer is extracted with ether the ether solution is washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water is then dried The ether filtrate is concentrated with 200 g silica-gel is added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To polyphosphoric acid (932 g ) at 70° C. on the steam bath is added p-fluoro-α-methylhydrocinnamic acid (93.2 g., 0.5 mole) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at that temperature for 1 hour. The mixture is allowed to cool and added to 2 l. of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 g. silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. to cool added to 2 l The aqueous layer is extracted with ether the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water dried The ether filtrate is concentrated with 200 g silica-gel, and added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To polyphosphoric acid (932 g ) at 70° C. on the steam bath is added p-fluoro-α-methylhydrocinnamic acid (93.2 g., 0.5 mole) slowly with stirring. The temperature is gradually raised to 95° C., and the mixture is kept at that temperature for 1 hour. The mixture is allowed to cool and added to 2 l. of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water, and then dried. The ether filtrate is concentrated with 200 g. silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5-10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. to cool added to 2 l The aqueous layer is extracted with ether the ether solution washed twice with saturated sodium chloride solution, 5% Na2CO3 solution, water dried The ether filtrate is concentrated with 200 g silica-gel, and added to a five pound silica-gel column The column is eluted with 5-10% ether-petroleum ether