2-(4-methylsulfanylphenyl)acetyl chloride

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)-2-[4-(methylthio)phenyl]-ethan-1-one was prepared by Friedel Crafts acylation of 2-fluoroanisole with 4-(methylthio)phenylacetyl chloride in the presence of aluminum chloride: 1H NMR (CDCl3 /300 MHz) δ 7.80-7.70 (m, 2H), 7.24-7.15 (m, 4H), 6.98 (t, J=8.26 Hz), 4.17 (s, 2H), 3.95 (s, 3H), 2.46 (s, 3H). 19F NMR (CDCl3 /282.2 MHz): -134.804 (m).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thereafter 174 g (1.3 moles) of anhydrous aluminum chloride was suspended in 600 ml of fluorobenzene. To the suspension was added dropwise a solution of 175 g of 4-methylthiophenylacetyl chloride obtained in the same manner as above in 120 ml of fluorobenzene at a temperature of 0° to 3° C. The resulting mixture was stirred at 20° C. for 3.5 hours. Then the reaction mixture was gradually poured into a mixture of ice water and hydrochloric acid, followed by extraction with dichloromethane. The dichloromethane layer was washed sequentially with a 5% aqueous solution of sodium bicarbonate and a saturated saline solution and dried over magnesium sulfate. The dichloromethane was distilled off and the resulting crystals were dissolved in 300 ml of a 2:1 mixture of ethyl acetate and isopropyl ether with heating. Ten grams of activated carbon was added and the solution was filtered. The separated crystals were collected by filtration, giving 92 g (40%) of 1-(4-fluorophenyl)-2-(4-methylthiophenyl)ethanone as pale yellow solids. followed by extraction with dichloromethane The dichloromethane layer was washed sequentially with a 5% aqueous solution of sodium bicarbonate a saturated saline solution and dried over magnesium sulfate The dichloromethane was distilled off the resulting crystals were dissolved in 300 ml of a 2:1 mixture of ethyl acetate and isopropyl ether with heating Ten grams of activated carbon was added the solution was filtered The separated crystals were collected by filtration

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thereafter 174 g (1.3 moles) of anhydrous aluminum chloride was suspended in 600 ml of fluorobenzene. To the suspension was added dropwise a solution of 175 g of 4-methylthiophenylacetyl chloride obtained in the same manner as above in 120 ml of fluorobenzene at a temperature of 0° to 3° C. The resulting mixture was stirred at 20° C. for 3.5 hours. Then the reaction mixture was gradually poured into a mixture of ice water and hydrochloric acid, followed by extraction with dichloromethane. The dichloromethane layer was washed sequentially with a 5% aqueous solution of sodium bicarbonate and a saturated saline solution and dried over magnesium sulfate. The dichloromethane was distilled off and the resulting crystals were dissolved in 300 ml of a 2:1 mixture of ethyl acetate and isopropyl ether with heating. Ten grams of activated carbon was added and the solution was filtered. The separated crystals were collected by filtration, giving 92 g (40%) of 1-(4-fluorophenyl)-2-(4-methylthiophenyl)ethanone as pale yellow solids. followed by extraction with dichloromethane The dichloromethane layer was washed sequentially with a 5% aqueous solution of sodium bicarbonate a saturated saline solution and dried over magnesium sulfate The dichloromethane was distilled off the resulting crystals were dissolved in 300 ml of a 2:1 mixture of ethyl acetate and isopropyl ether with heating Ten grams of activated carbon was added the solution was filtered The separated crystals were collected by filtration

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 158 g (0.87 mole) of 4-methylthiophenylacetic acid and 150 ml (2 moles) of thionyl chloride was heated at 90° C. for 2 hours. After completion of the reaction, an excess of thionyl chloride was distilled off under reduced pressure, giving about 120 g of 4-methylthiophenylacetyl chloride as a black oily product. The oily product thus obtained was subjected to the subsequent reaction without isolation and purification. After completion of the reaction an excess of thionyl chloride was distilled off under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of fluorobenzene (181 mL) and aluminum chloride (18.5 g, 139 mmol) was treated with a solution of 4-methylthiophenyl acetic chloride (21.9 g, 120 mmol) in 37 mL of fluorobenzene. When the addition was completed, the mixture was stirred at 50° C. for 3 h. The reaction mixture was then poured into ice water and stirred for 1 h. It was extracted with chloroform and washed with 5% aqueous sodium bicarbonate solution and with brine. The organic layer was separated and dried over anhydrous sodium sulfate. The drying agent was filtered and the filtrate concentrated in vacuum to give 15.6 g (55%) of the desired compound as a yellow solid. When the addition stirred for 1 h It was extracted with chloroform washed with 5% aqueous sodium bicarbonate solution and with brine The organic layer was separated dried over anhydrous sodium sulfate The drying agent was filtered the filtrate concentrated in vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of fluorobenzene (181 mL) and aluminum chloride (18.5 g, 139 mmol) was treated with a solution of 4-methylthiophenyl acetic chloride (21.9 g, 120 mmol) in 37 mL of fluorobenzene. When the addition was completed, the mixture was stirred at 50° C. for 3 h. The reaction mixture was then poured into ice water and stirred for 1 h. It was extracted with chloroform and washed with 5% aqueous sodium bicarbonate solution and with brine. The organic layer was separated and dried over anhydrous sodium sulfate. The drying agent was filtered and the filtrate concentrated in vacuum to give 15.6 g (55%) of the desired compound as a yellow solid. When the addition stirred for 1 h It was extracted with chloroform washed with 5% aqueous sodium bicarbonate solution and with brine The organic layer was separated dried over anhydrous sodium sulfate The drying agent was filtered the filtrate concentrated in vacuum

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)-2-[4-(methylthio)phenyl]-ethan-1-one was prepared by Friedel Crafts acylation of 2-fluoroanisole with 4-(methylthio)phenylacetyl chloride in the presence of aluminum chloride: 1H NMR (CDCl3 /300 MHz) δ 7.80-7.70 (m, 2H), 7.24-7.15 (m, 4H), 6.98 (t, J=8.26 Hz), 4.17 (s, 2H), 3.95 (s, 3H), 2.46 (s, 3H). 19F NMR (CDCl3 /282.2 MHz): -134.804 (m).

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

Procedure: The procedure described in Example 17 was repeated, but using 1.0 g of 3-(pyrrolidin-1-ylmethyl)thiomorpholine, 1.38 ml of triethylamine and 1.2 of 4-methylthiophenylacetyl chloride, to afford 1.38 g of the title compound, melting at 162°-166° C. (dec.).

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)-2-[4-(methylthio)phenyl]-ethan-1-one was prepared by Friedel Crafts acylation of 2-fluoroanisole with 4-(methylthio)phenylacetyl chloride in the presence of aluminum chloride: 1H NMR (CDCl3 /300 MHz) δ 7.80-7.70 (m, 2H), 7.24-7.15 (m, 4H), 6.98 (t, J=8.26 Hz), 4.17 (s, 2H), 3.95 (s, 3H), 2.46 (s, 3H). 19F NMR (CDCl3 /282.2 MHz): -134.804 (m).

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

Procedure: The procedure described in Example 17 was repeated, but using 1.0 g of 3-(pyrrolidin-1-ylmethyl)thiomorpholine, 1.38 ml of triethylamine and 1.2 of 4-methylthiophenylacetyl chloride, to afford 1.38 g of the title compound, melting at 162°-166° C. (dec.).

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)-2-[4-(methylthio)phenyl]-ethan-1-one was prepared by Friedel Crafts acylation of 2-fluoroanisole with 4-(methylthio)phenylacetyl chloride in the presence of aluminum chloride: 1H NMR (CDCl3 /300 MHz) δ 7.80-7.70 (m, 2H), 7.24-7.15 (m, 4H), 6.98 (t, J=8.26 Hz), 4.17 (s, 2H), 3.95 (s, 3H), 2.46 (s, 3H). 19F NMR (CDCl3 /282.2 MHz): -134.804 (m).

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

Procedure: The procedure described in Example 17 was repeated, but using 1.0 g of 3-(pyrrolidin-1-ylmethyl)thiomorpholine, 1.38 ml of triethylamine and 1.2 of 4-methylthiophenylacetyl chloride, to afford 1.38 g of the title compound, melting at 162°-166° C. (dec.).