4-chloro-N-phenylbutanamide

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

Procedure: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.8 g (0.024 mole) of 4-chloro-N-phenylbutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.3 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was heated on a steam bath for 16 h. The mixture was poured into 1 L of water and extracted thrice with 100 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a viscous oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column, eluted with 10% methanol in methylene chloride. The fractions containing the desired product were combined and concentrated under reduced pressure to give a foam. The foam was converted to the oxalic acid salt, and the solid was recrystallized from 2-propanol to yield 3.0 g (26 %) of the title compound as a white solid, mp 145°-147° C. was heated on a steam bath for 16 h extracted thrice with 100 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a viscous oil The oil was purified by column chromatography eluted with 10% methanol in methylene chloride The fractions containing the desired product concentrated under reduced pressure to give a foam the solid was recrystallized from 2-propanol

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

Procedure: A solution of 27.9 g (0.30 mole) of aniline in 100 ml of tetrahydrofuran was added dropwise to a solution of 21.2 g (0.15 mole) of 4-chlorobutyryl chloride in 100 ml of tetrahydrofuran. The reaction mixture was stirred mechanically and the temperature maintained between 5° C. and 15° C. throughout the addition. After the final addition, the solution was filtered to remove solid precipitates and the filtrate was concentrated under reduced pressure to yield 28.9 g (100%) of yellow solid. An analytical sample was prepared by recrystallizing the solid from benzene/petroleum ether (30°-60° C.) to give a white solid, mp 64°-66° C. the temperature maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate was concentrated under reduced pressure

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

Procedure: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.8 g (0.024 mole) of 4-chloro-N-phenylbutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.3 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was heated on a steam bath for 16 h. The mixture was poured into 1 L of water and extracted thrice with 100 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a viscous oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column, eluted with 10% methanol in methylene chloride. The fractions containing the desired product were combined and concentrated under reduced pressure to give a foam. The foam was converted to the oxalic acid salt, and the solid was recrystallized from 2-propanol to yield 3.0 g (26 %) of the title compound as a white solid, mp 145°-147° C. was heated on a steam bath for 16 h extracted thrice with 100 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a viscous oil The oil was purified by column chromatography eluted with 10% methanol in methylene chloride The fractions containing the desired product concentrated under reduced pressure to give a foam the solid was recrystallized from 2-propanol

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

Procedure: A solution of 27.9 g (0.30 mole) of aniline in 100 ml of tetrahydrofuran was added dropwise to a solution of 21.2 g (0.15 mole) of 4-chlorobutyryl chloride in 100 ml of tetrahydrofuran. The reaction mixture was stirred mechanically and the temperature maintained between 5° C. and 15° C. throughout the addition. After the final addition, the solution was filtered to remove solid precipitates and the filtrate was concentrated under reduced pressure to yield 28.9 g (100%) of yellow solid. An analytical sample was prepared by recrystallizing the solid from benzene/petroleum ether (30°-60° C.) to give a white solid, mp 64°-66° C. the temperature maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate was concentrated under reduced pressure

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

Procedure: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.8 g (0.024 mole) of 4-chloro-N-phenylbutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.3 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was heated on a steam bath for 16 h. The mixture was poured into 1 L of water and extracted thrice with 100 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a viscous oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column, eluted with 10% methanol in methylene chloride. The fractions containing the desired product were combined and concentrated under reduced pressure to give a foam. The foam was converted to the oxalic acid salt, and the solid was recrystallized from 2-propanol to yield 3.0 g (26 %) of the title compound as a white solid, mp 145°-147° C. was heated on a steam bath for 16 h extracted thrice with 100 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a viscous oil The oil was purified by column chromatography eluted with 10% methanol in methylene chloride The fractions containing the desired product concentrated under reduced pressure to give a foam the solid was recrystallized from 2-propanol

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

Procedure: A solution of 27.9 g (0.30 mole) of aniline in 100 ml of tetrahydrofuran was added dropwise to a solution of 21.2 g (0.15 mole) of 4-chlorobutyryl chloride in 100 ml of tetrahydrofuran. The reaction mixture was stirred mechanically and the temperature maintained between 5° C. and 15° C. throughout the addition. After the final addition, the solution was filtered to remove solid precipitates and the filtrate was concentrated under reduced pressure to yield 28.9 g (100%) of yellow solid. An analytical sample was prepared by recrystallizing the solid from benzene/petroleum ether (30°-60° C.) to give a white solid, mp 64°-66° C. the temperature maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate was concentrated under reduced pressure