4-chloro-1-(4-chlorophenyl)butan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 358 g of bromine in 350 ml of methylene chloride is added dropwise to a solution of 483 g (2.23 mols) of 4-chlorophenyl 3-chloropropyl ketone in 1200 ml of methylene chloride at 20° C. Stirring is continued for one hour and the mixture is then evaporated down in vacuo. 300 ml of petroleum ether are added to the residue, and stirring is continued until crystallization is complete. The mixture is cooled to 10° C., and the precipitate is filtered off under suction. 582 g (88.3% of theory) of 4-chlorophenyl 1-bromo-3-chloropropyl ketone of melting point 73° C. are obtained. the mixture is then evaporated down in vacuo 300 ml of petroleum ether are added to the residue stirring is continued until crystallization the precipitate is filtered off under suction

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

Procedure: Thiosemicarbazide (9.11 g, 0.1 mol) was added under nitrogen to a solution of 4,4'-dichlorobutyrophenone (21.7 g, 0.1 mol) in 350 mL of methanol plus 27 mL of 1N HCl plus 25 mL of water and the reaction stirred at room temperature for 21 hours (overnight). The solid was collected by filtration and dried to give 20.23 g of a white solid. Recrystallization of the solid from isopropyl alcohol gave 8.37 g (29%) of the title compound as a light yellow solid, mp 125-126° C. The solid was collected by filtration dried

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

Procedure: A solution of 4,4'-dichlorobutyrophenone (4.5 g, 20.7 mmole) in 25 ml of acetone was added to a warm suspension of 2-chloro-4-(1-piperazinyl)benzenemethanol (4.7 g, 20.7 mole) in 50 ml acetone and 2.5 ml of triethylamine. The reaction mixture was refluxed for four days, cooled at -10° for three hours, and then filtered. The product was washed with a little acetone, triturated on the filter with water (four times, 50 ml), and air dried. Recrystallization from acetonitrile (65 ml) gave 3.0 g (35%), mp 137°-139°. The reaction mixture was refluxed for four days cooled at -10° for three hours filtered The product was washed with a little acetone triturated on the filter with water (four times, 50 ml), and air dried Recrystallization from acetonitrile (65 ml) gave 3.0 g (35%), mp 137°-139°

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

Procedure: To a 0° C. slurry of 10.5 g. of imidazole in 15 ml. dry dimethylformamide was added 6.5 g. of γ,p-dichlorobutyrophenone and the mixture was stirred overnight at room temperature then one day at 60° C. The above solution was poured into 400 ml. of water and extracted three times with ethyl acetate. The combined extracts were washed with water, dried over magnesium sulfate and the solvent evaporated to afford 1-[4-(4-chlorophenyl)butan-4-onyl]imidazole, which was used in the next step. This material may be further purified, if necessary, through the nitrate salt. To a 0° C. one day at 60° C The above solution was poured into 400 ml of water and extracted three times with ethyl acetate The combined extracts were washed with water dried over magnesium sulfate the solvent evaporated