3,5-dichloro-4-hydroxybenzonitrile

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

Procedure: 10 g (0.092 mol) of α-fluoroacryloyl chloride (obtained in accordance with example 1c) were added dropwise, at a temperature of 5° C., with stirring and in the course of 20 minutes, to a solution of 16.7 g (0.089 mol) of 3,5-dichloro-4-hydroxybenzonitrile and 9 g (0.089 mol) of triethylamine in 200 ml of anhydrous methylene dichloride, and the reaction mixture was then stirred for a further 30 minutes at the same temperature. The solid formed was filtered off and washed with 20 ml of anhydrous methylene dichloride. After 0.005 g of hydroquinone monomethyl ether had been added, the volatile constituents in the mixture of filtrate and wash solution were removed by distillation, and the residue was recrystallized from boiling n-heptane. 18.7 g (81% of theory) of 2,6-dichloro-4-cyanophenyl α-fluoroacrylate were obtained, melting point 95° to 99° C. The solid formed was filtered off washed with 20 ml of anhydrous methylene dichloride After 0.005 g of hydroquinone monomethyl ether had been added the volatile constituents in the mixture of filtrate wash solution were removed by distillation the residue was recrystallized

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

Procedure: 10 g (0.092 mol) of α-fluoroacryloyl chloride (obtained in accordance with example 1c) were added dropwise, at a temperature of 5° C., with stirring and in the course of 20 minutes, to a solution of 16.7 g (0.089 mol) of 3,5-dichloro-4-hydroxybenzonitrile and 9 g (0.089 mol) of triethylamine in 200 ml of anhydrous methylene dichloride, and the reaction mixture was then stirred for a further 30 minutes at the same temperature. The solid formed was filtered off and washed with 20 ml of anhydrous methylene dichloride. After 0.005 g of hydroquinone monomethyl ether had been added, the volatile constituents in the mixture of filtrate and wash solution were removed by distillation, and the residue was recrystallized from boiling n-heptane. 18.7 g (81% of theory) of 2,6-dichloro-4-cyanophenyl α-fluoroacrylate were obtained, melting point 95° to 99° C. The solid formed was filtered off washed with 20 ml of anhydrous methylene dichloride After 0.005 g of hydroquinone monomethyl ether had been added the volatile constituents in the mixture of filtrate wash solution were removed by distillation the residue was recrystallized

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

Procedure: 5-[5-(2,6-Dichloro-4-cyanophenoxy)pentyl]-3-methylisoxazole [IX; Y=(CH2)5, Z=N, R=CH3, R1 =2-Cl, R2 =6-Cl] was prepared from 13.4 g 3,5-dichloro-4-hydroxybenzonitrile, 23.2 g 5-(5-bromopentyl)-3-methylisoxazole, 20.7 g potassium carbonate and 15 g sodium iodide in 250 ml dimethylformamide, similar to the procedure of Example 1, and was obtained in the form of colorless crystals (11.6 g), m.p. 59°-60° C. (from tertiary-butyl methyl ether-hexane).

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

Procedure: 10 g (0.092 mol) of α-fluoroacryloyl chloride (obtained in accordance with example 1c) were added dropwise, at a temperature of 5° C., with stirring and in the course of 20 minutes, to a solution of 16.7 g (0.089 mol) of 3,5-dichloro-4-hydroxybenzonitrile and 9 g (0.089 mol) of triethylamine in 200 ml of anhydrous methylene dichloride, and the reaction mixture was then stirred for a further 30 minutes at the same temperature. The solid formed was filtered off and washed with 20 ml of anhydrous methylene dichloride. After 0.005 g of hydroquinone monomethyl ether had been added, the volatile constituents in the mixture of filtrate and wash solution were removed by distillation, and the residue was recrystallized from boiling n-heptane. 18.7 g (81% of theory) of 2,6-dichloro-4-cyanophenyl α-fluoroacrylate were obtained, melting point 95° to 99° C. The solid formed was filtered off washed with 20 ml of anhydrous methylene dichloride After 0.005 g of hydroquinone monomethyl ether had been added the volatile constituents in the mixture of filtrate wash solution were removed by distillation the residue was recrystallized

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

Procedure: 5-[5-(2,6-Dichloro-4-cyanophenoxy)pentyl]-3-methylisoxazole [IX; Y=(CH2)5, Z=N, R=CH3, R1 =2-Cl, R2 =6-Cl] was prepared from 13.4 g 3,5-dichloro-4-hydroxybenzonitrile, 23.2 g 5-(5-bromopentyl)-3-methylisoxazole, 20.7 g potassium carbonate and 15 g sodium iodide in 250 ml dimethylformamide, similar to the procedure of Example 4, and was obtained in the form of colorless crystals (11.6 g), m.p. 59-60° C. (from tertiary-butyl methyl ether-hexane).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 10.0 g 3,5-dichloro-4-hydroxybenzonitrile, 6.2 mls 5-chloro-1-pentyne, 18.38 g milled potassium carbonate (100%) and 0.88 g potassium iodide in 125 mls N-methylpyrrolidone was heated at 60° C. with stirring overnight. An additional 4.6 g milled potassium carbonate and 2.82 mls 5-chloro-1-pentyne was added and heating was continued for two days. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate extracts were washed with aqueous 10% potassium bisulfate solution, water and saturated sodium chloride solution, dried (MgSO4) and concentrated in vacuo. The resulting oily residue was subjected to flash chromatography (silica gel; 10:90 ethyl acetate/hexane) to yield 7.03 g of the title compound. was added heating was continued for two days extracted with ethyl acetate The ethyl acetate extracts were washed with aqueous 10% potassium bisulfate solution, water and saturated sodium chloride solution dried (MgSO4) concentrated in vacuo

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

Procedure: 5-[5-(2,6-Dichloro-4-cyanophenoxy)pentyl]-3-methylisoxazole [IX; Y=(CH2)5, Z=N, R=CH3, R1 =2-Cl, R2 =6-Cl] was prepared from 13.4 g 3,5-dichloro-4-hydroxybenzonitrile, 23.2 g 5-(5-bromopentyl)-3-methylisoxazole, 20.7 g potassium carbonate and 15 g sodium iodide in 250 ml dimethylformamide, similar to the procedure of Example 1, and was obtained in the form of colorless crystals (11.6 g), m.p. 59°-60° C. (from tertiary-butyl methyl ether-hexane).

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

Procedure: 10 g (0.092 mol) of α-fluoroacryloyl chloride (obtained in accordance with example 1c) were added dropwise, at a temperature of 5° C., with stirring and in the course of 20 minutes, to a solution of 16.7 g (0.089 mol) of 3,5-dichloro-4-hydroxybenzonitrile and 9 g (0.089 mol) of triethylamine in 200 ml of anhydrous methylene dichloride, and the reaction mixture was then stirred for a further 30 minutes at the same temperature. The solid formed was filtered off and washed with 20 ml of anhydrous methylene dichloride. After 0.005 g of hydroquinone monomethyl ether had been added, the volatile constituents in the mixture of filtrate and wash solution were removed by distillation, and the residue was recrystallized from boiling n-heptane. 18.7 g (81% of theory) of 2,6-dichloro-4-cyanophenyl α-fluoroacrylate were obtained, melting point 95° to 99° C. The solid formed was filtered off washed with 20 ml of anhydrous methylene dichloride After 0.005 g of hydroquinone monomethyl ether had been added the volatile constituents in the mixture of filtrate wash solution were removed by distillation the residue was recrystallized