2-methoxyethanethiol

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

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

Procedure: 3.6 of 2-methoxyethyl-mercaptan is added dropwise to a mixture of 3.5 g of 55% sodium hydride and 80 ml of dimethylformamide. To this mixture 8.0 of 2-fluorophenylsulfonamide are added. The reaction mixture is stirred for 3 hours at a temperatur of 115°-120° C. After cooling the mixture is poured into water. To this mixture 10% of hydrochlorid acid are added, and the product is extracted with ethyl acetate. The organic phase is evaporated and the residue is purified by chromatography. Yield: 6.7 g of 2-methoxyethylthio-phenylsulfonamide, m.p. 119°-121° C. After cooling the mixture the product is extracted with ethyl acetate The organic phase is evaporated the residue is purified by chromatography

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

Procedure: To a solution of 2-chloro-2',4'-difluoroacetophenone (2.7 g, 0.014 mol) and 2-methoxyethanethiol (J. Med. Chem., 39, 1253(1996)) (1.4 g, 0.015 mol) in methanol (50 ml), potassium carbonate (2.3 g, 0.016 mol) was added under ice cooling, followed by stirring at room temperature for 30 minutes. After the completion of the reaction, the insoluble matter was filtered off and the filtrate was distilled off under reduced pressure. The residue so obtained was diluted with ether, washed with water, dried over magnesium sulfate and distilled off under reduced pressure, whereby 2',4'-difluoro-2-(2-methoxyethyl)thioacetophenone (2.3 g, yield: 67.0%) was obtained as a colorless oil. After the completion of the reaction the insoluble matter was filtered off the filtrate was distilled off under reduced pressure The residue so obtained washed with water dried over magnesium sulfate distilled off under reduced pressure

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

Procedure: To a solution of 2-chloro-2',4'-difluoroacetophenone (2.7 g, 0.014 mol) and 2-methoxyethanethiol (J. Med. Chem., 39, 1253(1996)) (1.4 g, 0.015 mol) in methanol (50 ml), potassium carbonate (2.3 g, 0.016 mol) was added under ice cooling, followed by stirring at room temperature for 30 minutes. After the completion of the reaction, the insoluble matter was filtered off and the filtrate was distilled off under reduced pressure. The residue so obtained was diluted with ether, washed with water, dried over magnesium sulfate and distilled off under reduced pressure, whereby 2',4'-difluoro-2-(2-methoxyethyl)thioacetophenone (2.3 g, yield: 67.0%) was obtained as a colorless oil. After the completion of the reaction the insoluble matter was filtered off the filtrate was distilled off under reduced pressure The residue so obtained washed with water dried over magnesium sulfate distilled off under reduced pressure

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

Procedure: 1.45 g (6.53 mmol) of 3-fluoro-2-methyl-4-trifluoromethylbenzoic acid were initially charged in 40 ml of DMF. 809 mg (20.2 mmol) of NaH were added a little at a time. After the evolution of gas had ceased, 1.20 g (13.1 mmol) of 2-methoxyethanethiol were added a little at a time. The mixture was stirred at RT for 10 minutes and then heated at 80° C. for 15 h. The reaction mixture was cooled and concentrated under reduced pressure, and for work-up water was added and the mixture was acidified with 1M HCl. The product precipitated and was removed by filtration. The product was then washed with water and n-heptane. What was isolated were 1.7 g of the pure product. heated at 80° C. for 15 h The reaction mixture was cooled concentrated under reduced pressure for work-up water was added The product precipitated was removed by filtration The product was then washed with water and n-heptane What was isolated

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

Procedure: 1.45 g (6.53 mmol) of 3-fluoro-2-methyl-4-trifluoromethylbenzoic acid were initially charged in 40 ml of DMF. 809 mg (20.2 mmol) of NaH were added a little at a time. After the evolution of gas had ceased, 1.20 g (13.1 mmol) of 2-methoxyethanethiol were added a little at a time. The mixture was stirred at RT for 10 minutes and then heated at 80° C. for 15 h. The reaction mixture was cooled and concentrated under reduced pressure, and for work-up water was added and the mixture was acidified with 1M HCl. The product precipitated and was removed by filtration. The product was then washed with water and n-heptane. What was isolated were 1.7 g of the pure product. heated at 80° C. for 15 h The reaction mixture was cooled concentrated under reduced pressure for work-up water was added The product precipitated was removed by filtration The product was then washed with water and n-heptane What was isolated

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

Procedure: 5.0 g (19.8 mmol) of 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid (synthesis described in WO 98/42648) were taken up in 40 ml of DMF. 871 mg (21.8 mmol, purity 60% by weight) of NaH were added. The mixture was stirred at RT for 30 minutes. A reaction mixture containing the sodium salt of 2-methoxyethanethiol (prepared from a solution of 2.19 g (23.7 mmol) of 2-methoxyethanethiol in 10 ml of DMF which had been added dropwise to a suspension of 950 mg (23.7 mmol, purity 60% by weight) of NaH in 30 ml of DMF, followed by stirring at RT for 30 minutes) was then added a little at a time. During the addition, the temperature was kept below 30° C. The reaction mixture was stirred at RT for 16 h, for work-up diluted with water and washed with diethyl ether. The aqueous phase was acidified with 1M HCl and extracted with tert-butyl methyl ether. The organic phase was dried and filtered. The aqueous phase was additionally extracted with EA, and the organic phase was also dried and filtered. The filtrates of the organic phases were combined and freed from the solvent. The residue was dried under reduced pressure and purified chromatographically. This gave 4.8 g of the pure product. by stirring at RT for 30 minutes) was then added a little at a time During the addition was kept below 30° C The reaction mixture was stirred at RT for 16 h, for work-up washed with diethyl ether extracted with tert-butyl methyl ether The organic phase was dried filtered The aqueous phase was additionally extracted with EA the organic phase was also dried filtered The residue was dried under reduced pressure purified chromatographically

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

Procedure: 5.0 g (19.8 mmol) of 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid (synthesis described in WO 98/42648) were taken up in 40 ml of DMF. 871 mg (21.8 mmol, purity 60% by weight) of NaH were added. The mixture was stirred at RT for 30 minutes. A reaction mixture containing the sodium salt of 2-methoxyethanethiol (prepared from a solution of 2.19 g (23.7 mmol) of 2-methoxyethanethiol in 10 ml of DMF which had been added dropwise to a suspension of 950 mg (23.7 mmol, purity 60% by weight) of NaH in 30 ml of DMF, followed by stirring at RT for 30 minutes) was then added a little at a time. During the addition, the temperature was kept below 30° C. The reaction mixture was stirred at RT for 16 h, for work-up diluted with water and washed with diethyl ether. The aqueous phase was acidified with 1M HCl and extracted with tert-butyl methyl ether. The organic phase was dried and filtered. The aqueous phase was additionally extracted with EA, and the organic phase was also dried and filtered. The filtrates of the organic phases were combined and freed from the solvent. The residue was dried under reduced pressure and purified chromatographically. This gave 4.8 g of the pure product. by stirring at RT for 30 minutes) was then added a little at a time During the addition was kept below 30° C The reaction mixture was stirred at RT for 16 h, for work-up washed with diethyl ether extracted with tert-butyl methyl ether The organic phase was dried filtered The aqueous phase was additionally extracted with EA the organic phase was also dried filtered The residue was dried under reduced pressure purified chromatographically

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

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

Procedure: 3.6 of 2-methoxyethyl-mercaptan is added dropwise to a mixture of 3.5 g of 55% sodium hydride and 80 ml of dimethylformamide. To this mixture 8.0 of 2-fluorophenylsulfonamide are added. The reaction mixture is stirred for 3 hours at a temperatur of 115°-120° C. After cooling the mixture is poured into water. To this mixture 10% of hydrochlorid acid are added, and the product is extracted with ethyl acetate. The organic phase is evaporated and the residue is purified by chromatography. Yield: 6.7 g of 2-methoxyethylthio-phenylsulfonamide, m.p. 119°-121° C. After cooling the mixture the product is extracted with ethyl acetate The organic phase is evaporated the residue is purified by chromatography

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

Procedure: To a solution of 2-chloro-2',4'-difluoroacetophenone (2.7 g, 0.014 mol) and 2-methoxyethanethiol (J. Med. Chem., 39, 1253(1996)) (1.4 g, 0.015 mol) in methanol (50 ml), potassium carbonate (2.3 g, 0.016 mol) was added under ice cooling, followed by stirring at room temperature for 30 minutes. After the completion of the reaction, the insoluble matter was filtered off and the filtrate was distilled off under reduced pressure. The residue so obtained was diluted with ether, washed with water, dried over magnesium sulfate and distilled off under reduced pressure, whereby 2',4'-difluoro-2-(2-methoxyethyl)thioacetophenone (2.3 g, yield: 67.0%) was obtained as a colorless oil. After the completion of the reaction the insoluble matter was filtered off the filtrate was distilled off under reduced pressure The residue so obtained washed with water dried over magnesium sulfate distilled off under reduced pressure

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

Procedure: 1.45 g (6.53 mmol) of 3-fluoro-2-methyl-4-trifluoromethylbenzoic acid were initially charged in 40 ml of DMF. 809 mg (20.2 mmol) of NaH were added a little at a time. After the evolution of gas had ceased, 1.20 g (13.1 mmol) of 2-methoxyethanethiol were added a little at a time. The mixture was stirred at RT for 10 minutes and then heated at 80° C. for 15 h. The reaction mixture was cooled and concentrated under reduced pressure, and for work-up water was added and the mixture was acidified with 1M HCl. The product precipitated and was removed by filtration. The product was then washed with water and n-heptane. What was isolated were 1.7 g of the pure product. heated at 80° C. for 15 h The reaction mixture was cooled concentrated under reduced pressure for work-up water was added The product precipitated was removed by filtration The product was then washed with water and n-heptane What was isolated