4-chloropentanoyl chloride

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

実験手順: A mixture of 30 g. of γ -valerolactone, 30 ml. of distilled thionyl chloride and 0.5 g. of zinc chloride was heated on a steam bath overnight and then distilled at 15 mm. The distillate was redistilled at 69- 70° and 15 mm. giving 34 g. of 4-chlorovaleryl chloride. The acid chloride was reduced catalytically, reacted with 5-chlorosalicylhydroxamic acid and the resulting intermediate was ring-closed according to the method described in Example 3. The product after recrystallization from trichloroethylene weighed 8.5 g. and melted at 210- 213° C. A mixture of 30 g distilled at 15 mm The distillate was redistilled at 69- 70° giving 34 g the resulting intermediate was ring-closed The product after recrystallization from trichloroethylene

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

実験手順: A mixture of 30 g. of γ -valerolactone, 30 ml. of distilled thionyl chloride and 0.5 g. of zinc chloride was heated on a steam bath overnight and then distilled at 15 mm. The distillate was redistilled at 69- 70° and 15 mm. giving 34 g. of 4-chlorovaleryl chloride. The acid chloride was reduced catalytically, reacted with 5-chlorosalicylhydroxamic acid and the resulting intermediate was ring-closed according to the method described in Example 3. The product after recrystallization from trichloroethylene weighed 8.5 g. and melted at 210- 213° C. A mixture of 30 g distilled at 15 mm The distillate was redistilled at 69- 70° giving 34 g the resulting intermediate was ring-closed The product after recrystallization from trichloroethylene

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: At 0° C., a solution of 0.16 g (1.0 mmol) of 4-chloropentanoyl chloride in 15 ml dichloromethane is added to a solution of 0.20 g (1.0 mmol) of diphenylmethanone hydrazone and 0.08 ml of pyridine in 15 ml of dichloromethane. The reaction mixture is stirred at room temperature for 16 h. Ethyl acetate/saturated aqueous NH4Cl solution is added to the reaction mixture, the organic phase is separated off and the aqueous phase is extracted with 3×100 ml of ethyl acetate. The combined organic phases are dried over Na2SO4 and freed from the solvent under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 0.32 g (100%) of the desired product; log P(HCOOH): 3.76; 1H-NMR (ppm): δ (DMSO-d6)=1.45 (d, 0.9H), 1.52 (d, 2.1H), 1.81-2.12 (m, 1H), 2.30-2.42 (m, 1H), 2.88-3.00 (m, 2H), 4.13-4.20 (m, 0.3H), 4.28-4.34 (m, 0.7H), 7.26-7.61 (m, 10H), 9.19 (s, 1H); LC-MS: m/z=315 [M+H]+ the organic phase is separated off the aqueous phase is extracted with 3×100 ml of ethyl acetate The combined organic phases are dried over Na2SO4 Purification by column chromatography on silica gel (cyclohexane/ethyl acetate)

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

実験手順: Aluminum chloride (16 g, 0.12 mol) is suspended in carbon tetrachloride (80 ml). To the suspension is added dropwise 4-chlorovaleric acid chloride (18.6 g, 0.12 mol) with ice-cooling. The mixture is stirred for 15 minutes and benzene (7.8 g, 0.1 mol) is added dropwise to the mixture at below 5° C. Stirring is continued at the same temperature for 1 hour. The mixture is poured into ice-hydrochloric acid and extracted with chloroform. The chloroform layer is washed with water, saturated aqueous sodium bicarbonate, water and then saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. Chloroform is distilled off and the resulting crude crystals are recrystallized from hexane to obtain 4-chlorobutyl phenyl ketone (8.3 g) as colorless flakes, m.p. 49°-50° C. cooling Stirring is continued at the same temperature for 1 hour extracted with chloroform The chloroform layer is washed with water, saturated aqueous sodium bicarbonate, water saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate Chloroform is distilled off the resulting crude crystals are recrystallized from hexane

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reation mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated

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

実験手順: N-Benzylpiperazine (1.0 g, 5.7 mmole) and triethylamine (1.17 ml, 8.5 mmole) were combined in 20 ml of methylene chloride. 4-Chlorovaleryl chloride (0.945 ml, 8.5 mmole) in 10 ml of methylene chloride was added dropwise over 20 minutes and the reaction mixture stirred for 16 hours at room temperature. Water (20 ml) was then added and the organic layer dried (anhydrous magnesium sulfate) and evaporated in vacuo to a gum. The gum was chromatographed on silica gel with ethyl acetate as eluant and tlc monitoring. Clean product fractions were combined and evaporated to yield the title product as a gum [920 mg, Rf 0.5 (ethyl acetate)]. the organic layer dried (anhydrous magnesium sulfate) evaporated in vacuo to a gum The gum was chromatographed on silica gel with ethyl acetate as eluant evaporated