5-chloro-1-(4-fluorophenyl)pentan-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:

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

実験手順: A mixture of 19.3 g (0.07 mole) of α,α -diphenyl-4-piperidinemethanol, 17.1 g (0.08 mole) of 5-chloro-4'-fluorovalerophenone, 20.0 g (0.2 mole) of potassium bicarbonate, and 0.1 g of potassium iodide in 250 ml of toluene and 35 ml of water is stirred on a steam bath for 70 hours. The organic layer is separated and combined with two 50 ml toluene extracts of the aqueous layer. The combined organic material is washed with water and saturated sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate is diluted with about 200 ml of ether then made acidic with ethereal HCl. The resulting precipitate is recrystallized from methanol-butanone to give 4'-fluoro-5-[4-(α-hydroxy-α-phenylbenzyl)piperidino]valerophenone hydrochloride, M.P. 177°-179°C. The organic layer is separated The combined organic material is washed with water and saturated sodium chloride solution dried over magnesium sulfate filtered The filtrate is diluted with about 200 ml of ether The resulting precipitate is recrystallized from methanol-butanone

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

実験手順: A mixture of 19.3 g (0.07 mole) of α,α -diphenyl-4-piperidinemethanol, 17.1 g (0.08 mole) of 5-chloro-4'-fluorovalerophenone, 20.0 g (0.2 mole) of potassium bicarbonate, and 0.1 g of potassium iodide in 250 ml of toluene and 35 ml of water is stirred on a steam bath for 70 hours. The organic layer is separated and combined with two 50 ml toluene extracts of the aqueous layer. The combined organic material is washed with water and saturated sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate is diluted with about 200 ml of ether then made acidic with ethereal HCl. The resulting precipitate is recrystallized from methanol-butanone to give 4'-fluoro-5-[4-(α-hydroxy-α-phenylbenzyl)piperidino]valerophenone hydrochloride, M.P. 177°-179°C. The organic layer is separated The combined organic material is washed with water and saturated sodium chloride solution dried over magnesium sulfate filtered The filtrate is diluted with about 200 ml of ether The resulting precipitate is recrystallized from methanol-butanone

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

実験手順: According to Procedure B above, 6-chloro-4-(piperidin-4-ylamino)-chromen-2-one (0.025 g, 0.05 mmol) and 1-(4-fluorophenyl)-5-chloro-1-oxopentane (0.024 g, 0.11 mmol) were allowed to react to give the title compound (0.0078 g, 27.4%, mono-TFA salt) as a off-white solid. 1H NMR (300 MHz, MeOH) δ ppm 8.05-8.15 (m, 3H), 7.62 (dd, J=3, 9, 1H), 7.35 (d, J=9, 1H), 7.20-7.28 (m, 2H), 5.47 (s, 1H), 3.82-3.92 (m, 1H), 3.67-3.75 (m, 2H), 3.11-3.25 (m, 5H), 2.32-2.43 (m, 2H), 2.15-2.25 (m, 1H), 1.87-2.03 (m, 2H), 1.79-1.87 (m, 4H); MS (ESI+Q1MS) m/z 457 [M]+ to react

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

実験手順: According to Procedure B above, 6-chloro-4-(piperidin-4-ylamino)-chromen-2-one (0.025 g, 0.05 mmol) and 1-(4-fluorophenyl)-5-chloro-1-oxopentane (0.024 g, 0.11 mmol) were allowed to react to give the title compound (0.0078 g, 27.4%, mono-TFA salt) as a off-white solid. 1H NMR (300 MHz, MeOH) δ ppm 8.05-8.15 (m, 3H), 7.62 (dd, J=3, 9, 1H), 7.35 (d, J=9, 1H), 7.20-7.28 (m, 2H), 5.47 (s, 1H), 3.82-3.92 (m, 1H), 3.67-3.75 (m, 2H), 3.11-3.25 (m, 5H), 2.32-2.43 (m, 2H), 2.15-2.25 (m, 1H), 1.87-2.03 (m, 2H), 1.79-1.87 (m, 4H); MS (ESI+Q1MS) m/z 457 [M]+ to react

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

実験手順: A mixture of 19.3 g (0.07 mole) of α,α -diphenyl-4-piperidinemethanol, 17.1 g (0.08 mole) of 5-chloro-4'-fluorovalerophenone, 20.0 g (0.2 mole) of potassium bicarbonate, and 0.1 g of potassium iodide in 250 ml of toluene and 35 ml of water is stirred on a steam bath for 70 hours. The organic layer is separated and combined with two 50 ml toluene extracts of the aqueous layer. The combined organic material is washed with water and saturated sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate is diluted with about 200 ml of ether then made acidic with ethereal HCl. The resulting precipitate is recrystallized from methanol-butanone to give 4'-fluoro-5-[4-(α-hydroxy-α-phenylbenzyl)piperidino]valerophenone hydrochloride, M.P. 177°-179°C. The organic layer is separated The combined organic material is washed with water and saturated sodium chloride solution dried over magnesium sulfate filtered The filtrate is diluted with about 200 ml of ether The resulting precipitate is recrystallized from methanol-butanone

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: Prepared by Procedure K and Scheme E using 5-chloro-1-(4-fluorophenyl)-1-pentanone and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 425.2 (M+H)+. Prepared by Procedure K and Scheme E