(2-chloro-6-fluorophenyl)methanol

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

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

Procedure: Particularly preferably, 2,6-dichlorobenzaldehyde is used in the process of the invention and 2-fluoro-6-chlorobenzaldehyde, 2-fluoro-6-chlorobenzyl alcohol, 2,6-difluorobenzaldehyde or 2,6-difluorobenzyl alcohol is obtained or 2,4-dichlorobenzaldehyde is used and 2,4-difluoro-benzaldehyde or 2,4-difluorobenzyl alcohol is obtained or 3,4-dichloro-benzaldehyde is used and 3-chloro-4-fluorobenzaldehyde or 3-chloro-4-fluorobenzyl alcohol is obtained.

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

Procedure: The title compound (cis/trans=21/79) was prepared as a pale brown powder in 57.60% yield in a similar procedure to that described in Example 1 by using 1-(2-butenyl)-7-chloro-2,3-dimethylpyrrolo[2,3-d]pyridazine (cis/trans=24/76) and 2-chloro-6-fluorobenzyl alcohol.

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

Procedure: Particularly preferably, 2,6-dichlorobenzaldehyde is used in the process of the invention and 2-fluoro-6-chlorobenzaldehyde, 2-fluoro-6-chlorobenzyl alcohol, 2,6-difluorobenzaldehyde or 2,6-difluorobenzyl alcohol is obtained or 2,4-dichlorobenzaldehyde is used and 2,4-difluoro-benzaldehyde or 2,4-difluorobenzyl alcohol is obtained or 3,4-dichloro-benzaldehyde is used and 3-chloro-4-fluorobenzaldehyde or 3-chloro-4-fluorobenzyl alcohol is obtained.

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

Procedure: 2-Chloro-6-fluorobenzyl alcohol (50 g) was stirred in dichloromethane and a solution of sodium hydroxide (32 g) in water was added. After 30 minutes stirring the mixture was cooled to 0° C. when dimethyl sulphate (47 g) and tetrabutyl-ammonium hydrogen-sulphate (1 g) were added dropwise. The mixture was allowed to warm to room temperature and stirred for 3 hours. It was quenched with water and extracted with dichloromethane. The organic extract was washed with water, dried (anhydrous magnesium sulphate) and filtered. The filtrate was evaporated to dryness and the residue distilled under reduced pressure yielding 1-chloro-3-fluoro-2-methoxymethylbenzene (27.3 g) b.p. 82°-95° C./24 mm Hg. were added dropwise stirred for 3 hours It was quenched with water extracted with dichloromethane The organic extract was washed with water dried (anhydrous magnesium sulphate) filtered The filtrate was evaporated to dryness the residue distilled under reduced pressure

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

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

Procedure: To a solution of (2-chloro-6-fluorophenyl)methanol (160.5 mg, 0.99 mmol) in THF (8 mL) was added sodium hydride (40 mg, 0.99 mmol) and the reaction was stirred at room temperature. After 25 minutes ethyl 1-(4-fluorophenyl)-2-iodo-1H-imidazole-5-carboxylate (38) (300 mg, 0.83 mmol) was added and the reaction was refluxed overnight. Water was added slowly and the solution was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford ethyl 2-((2-chloro-6-fluorobenzyl)oxy)-1-(4-fluorophenyl)-1H-imidazole-5-carboxylate (39). the reaction was refluxed overnight the solution was extracted with ethyl acetate The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo