4-chloro-N,N-dimethylbutanamide

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, 3.7 g (0.025 mole) of 4-chloro-N,N-dimethylbutanamide, 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 1.5 L of water and extracted thrice with 500 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 300 g of silica gel on a 65 cm×4 cm column, eluted with methanol-methylene chloride (1:15). Fractions containing the desired product were combined and concentrated under reduced pressure to give a viscous oil. The oil was converted to the oxalic acid salt and the solid was recrystallized from 2-propanol/ethyl acetate to yield 1.6 g (16%) of the title compound as a white solid, mp 156°-158° C. was heated on a steam bath for 16 h extracted thrice with 500 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 methanol-methylene chloride (1:15) Fractions containing the desired product concentrated under reduced pressure to give a viscous oil the solid was recrystallized from 2-propanol/ethyl acetate

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

Procedure: A solution of 50.0 g (1.11 mole) of dimethylamine in 100 ml of tetrahydrofuran was added dropwise to a solution of 28.2 (0.20 mole) of 4-chlorobutyryl chloride in 50 ml of tetrahydrofuran. The reaction mixture was stirred mechanically while the temperature was 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 concentrated under reduced pressure to yield 29.6 g (99%) of a yellow liquid. An analytical sample was prepared by filtering the liquid through a small bed of silica gel and eluting with ethyl acetate-hexane (1:1). The fractions containing the desired product were combined and concentrated under reduced pressure to give the title compound as a light-yellow liquid. was maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate concentrated under reduced pressure

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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, 3.7 g (0.025 mole) of 4-chloro-N,N-dimethylbutanamide, 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 1.5 L of water and extracted thrice with 500 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 300 g of silica gel on a 65 cm×4 cm column, eluted with methanol-methylene chloride (1:15). Fractions containing the desired product were combined and concentrated under reduced pressure to give a viscous oil. The oil was converted to the oxalic acid salt and the solid was recrystallized from 2-propanol/ethyl acetate to yield 1.6 g (16%) of the title compound as a white solid, mp 156°-158° C. was heated on a steam bath for 16 h extracted thrice with 500 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 methanol-methylene chloride (1:15) Fractions containing the desired product concentrated under reduced pressure to give a viscous oil the solid was recrystallized from 2-propanol/ethyl acetate

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

Procedure: A solution of 50.0 g (1.11 mole) of dimethylamine in 100 ml of tetrahydrofuran was added dropwise to a solution of 28.2 (0.20 mole) of 4-chlorobutyryl chloride in 50 ml of tetrahydrofuran. The reaction mixture was stirred mechanically while the temperature was 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 concentrated under reduced pressure to yield 29.6 g (99%) of a yellow liquid. An analytical sample was prepared by filtering the liquid through a small bed of silica gel and eluting with ethyl acetate-hexane (1:1). The fractions containing the desired product were combined and concentrated under reduced pressure to give the title compound as a light-yellow liquid. was maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate concentrated under reduced pressure

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

Procedure: A solution of 50.0 g (1.11 mole) of dimethylamine in 100 ml of tetrahydrofuran was added dropwise to a solution of 28.2 (0.20 mole) of 4-chlorobutyryl chloride in 50 ml of tetrahydrofuran. The reaction mixture was stirred mechanically while the temperature was 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 concentrated under reduced pressure to yield 29.6 g (99%) of a yellow liquid. An analytical sample was prepared by filtering the liquid through a small bed of silica gel and eluting with ethyl acetate-hexane (1:1). The fractions containing the desired product were combined and concentrated under reduced pressure to give the title compound as a light-yellow liquid. was maintained between 5° C. and 15° C. throughout the addition After the final addition the solution was filtered to remove solid precipitates the filtrate concentrated under reduced pressure

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 4-chloro-butyryl chloride (1.12 ml, 10.0 mmol) and dimethyl-amine hydrochloride (4.1 g, 50.0 mmol) in THF at 5° C. was added 2M NaOH (30 ml, 60.0 mmol) dropwise over 30 minutes while maintaining reaction temperature between 5-10° C. The reaction was stirred for additional 1.5 h and was concentrated, extracted with EtOAc (×2). The combined organic layer was washed with 1M HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo to yield the title compound as colorless oil (1.5 g, ˜100%). The crude was used without further purification. while maintaining reaction temperature between 5-10° C was concentrated extracted with EtOAc (×2) The combined organic layer was washed with 1M HCl (×2), brine dried over Na2SO4 concentrated in vacuo