fluoromethylsulfinylbenzene

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

Procedure: Monofluoromethyl phenyl sulfoxide (1.01 g, 6.38 mmol) of example 2 was dissolved in dry diethyl ether (15 mL) under an argon atmosphere. p-Xylene (0.87 mL, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (1.07 mL, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred, at the same temperature, until the reaction was complete. HBF4 in Et2O solution (54%, 1.76 mL, 2 eq) was added and then resulting mixture was stirred for 30 minutes. The solid was isolated by filtration and melt at rt. Saturated solution of NaHCO3 (30 mL) was added to the oily mixture. The resulting mixture was extracted with dichloromethane. The organic phase was dried with magnesium sulfate and concentrated to dryness. 1.486 g of a yellow oily solid was obtained. the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature resulting mixture was stirred for 30 minutes The solid was isolated by filtration melt at rt The resulting mixture was extracted with dichloromethane The organic phase was dried with magnesium sulfate concentrated to dryness

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

Procedure: Monofluoromethyl phenyl sulfoxide (645 mg, 4.08 mmol) of example 2 was dissolved in dry diethyl ether (15 ml) under argon atmosphere. O-xylene (0.54 ml, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.68 mL, 1.0 eq) was added slowly maintaining the same temperature. The mixture was stirred until the reaction was complete. HBF4 solution (54%, 1.12 mL, 2 eq) was added and the resulting suspension was stirred for 30 minutes. The precipitate tetrafluoroborate salt was isolated by filtration, washed with diethyl ether at 0° C. and dried. The desired product was obtained as a slightly yellow oily solid (1.729 g). the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature the resulting suspension was stirred for 30 minutes

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

Procedure: Fluoromethyl phenyl sulphide (85 g, 351.63 mmol) was added to a mixture of methanol (250 ml) and water (50 mL). The resulting mixture was cooled to a temperature between 0° C. and 5° C. NBS (75.10 g, 1.2 eq) was added in small portions maintaining the same temperature range. The reaction mixture was stirred until the reaction was complete, and then, was quenched with Na2SO3 solution (10%, 150 mL). The pH of the reaction mixture was adjusted to a value between 7 and 8 with NaHCO3 saturated solution. The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C. The residue was extracted with dichloromethane (200 mL, 300 mL). The combined organic layer was washed with water (2×300 mL) and concentrated to ⅓ of the volume. Heptane (50 mL) was added and the resulting mixture was concentrated again. The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70) to give 49.8 g (89.6%) of the desired product as colourless oil at rt, which is a white solid at −20° C. The resulting mixture was cooled to a temperature between 0° C. and 5° C maintaining the same temperature range was quenched with Na2SO3 solution (10%, 150 mL) The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C The residue was extracted with dichloromethane (200 mL, 300 mL) The combined organic layer was washed with water (2×300 mL) concentrated Heptane (50 mL) was added the resulting mixture was concentrated again The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70)

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

Procedure: Fluoromethyl phenyl sulphide (85 g, 351.63 mmol) was added to a mixture of methanol (250 ml) and water (50 mL). The resulting mixture was cooled to a temperature between 0° C. and 5° C. NBS (75.10 g, 1.2 eq) was added in small portions maintaining the same temperature range. The reaction mixture was stirred until the reaction was complete, and then, was quenched with Na2SO3 solution (10%, 150 mL). The pH of the reaction mixture was adjusted to a value between 7 and 8 with NaHCO3 saturated solution. The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C. The residue was extracted with dichloromethane (200 mL, 300 mL). The combined organic layer was washed with water (2×300 mL) and concentrated to ⅓ of the volume. Heptane (50 mL) was added and the resulting mixture was concentrated again. The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70) to give 49.8 g (89.6%) of the desired product as colourless oil at rt, which is a white solid at −20° C. The resulting mixture was cooled to a temperature between 0° C. and 5° C maintaining the same temperature range was quenched with Na2SO3 solution (10%, 150 mL) The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C The residue was extracted with dichloromethane (200 mL, 300 mL) The combined organic layer was washed with water (2×300 mL) concentrated Heptane (50 mL) was added the resulting mixture was concentrated again The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70)

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

Procedure: Monofluoromethyl phenyl sulfoxide (1.01 g, 6.38 mmol) of example 2 was dissolved in dry diethyl ether (15 mL) under an argon atmosphere. p-Xylene (0.87 mL, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (1.07 mL, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred, at the same temperature, until the reaction was complete. HBF4 in Et2O solution (54%, 1.76 mL, 2 eq) was added and then resulting mixture was stirred for 30 minutes. The solid was isolated by filtration and melt at rt. Saturated solution of NaHCO3 (30 mL) was added to the oily mixture. The resulting mixture was extracted with dichloromethane. The organic phase was dried with magnesium sulfate and concentrated to dryness. 1.486 g of a yellow oily solid was obtained. the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature resulting mixture was stirred for 30 minutes The solid was isolated by filtration melt at rt The resulting mixture was extracted with dichloromethane The organic phase was dried with magnesium sulfate concentrated to dryness

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

Procedure: Monofluoromethyl phenyl sulfoxide (645 mg, 4.08 mmol) of example 2 was dissolved in dry diethyl ether (15 ml) under argon atmosphere. O-xylene (0.54 ml, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.68 mL, 1.0 eq) was added slowly maintaining the same temperature. The mixture was stirred until the reaction was complete. HBF4 solution (54%, 1.12 mL, 2 eq) was added and the resulting suspension was stirred for 30 minutes. The precipitate tetrafluoroborate salt was isolated by filtration, washed with diethyl ether at 0° C. and dried. The desired product was obtained as a slightly yellow oily solid (1.729 g). the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature the resulting suspension was stirred for 30 minutes

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

Procedure: Fluoromethyl phenyl sulphide (85 g, 351.63 mmol) was added to a mixture of methanol (250 ml) and water (50 mL) The resulting mixture was cooled to a temperature between 0° C. and 5° C. NBS (75.10 g, 1.2 eq) was added in small portions maintaining the same temperature range. The reaction mixture was stirred until the reaction was complete, and then, was quenched with Na2SO3 solution (10%, 150 mL). The pH of the reaction mixture was adjusted to a value between 7 and 8 with NaHCO3 saturated solution. The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C. The residue was extracted with dichloromethane (200 mL, 300 mL). The combined organic layer was washed with water (2×300 mL) and concentrated to 1/3 of the volume. Heptane (50 mL) was added and the resulting mixture was concentrated again. The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70) to give 49.8 g (89.6%) of the desired product as colourless oil at rt, which is a white solid at −20° C. was cooled to a temperature between 0° C. and 5° C maintaining the same temperature range was quenched with Na2SO3 solution (10%, 150 mL) The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C The residue was extracted with dichloromethane (200 mL, 300 mL) The combined organic layer was washed with water (2×300 mL) concentrated to 1/3 of the volume Heptane (50 mL) was added the resulting mixture was concentrated again The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70)

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

Procedure: Monofluoromethyl phenyl sulfoxide (1.01 g, 6.38 mmol) of example 2 was dissolved in dry diethyl ether (15 mL) under an argon atmosphere. p-Xylene (0.87 mL, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (1.07 mL, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred, at the same temperature, until the reaction was complete. HBF4 in Et2O solution (54%, 1.76 mL, 2 eq) was added and then resulting mixture was stirred for 30 minutes. The solid was isolated by filtration and melt at rt. Saturated solution of NaHCO3 (30 mL) was added to the oily mixture. The resulting mixture was extracted with dichloromethane. The organic phase was dried with magnesium sulfate and concentrated to dryness. 1.486 g of a yellow oily solid was obtained. the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature resulting mixture was stirred for 30 minutes The solid was isolated by filtration melt at rt The resulting mixture was extracted with dichloromethane The organic phase was dried with magnesium sulfate concentrated to dryness

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

Procedure: Monofluoromethyl phenyl sulfoxide (645 mg, 4.08 mmol) of example 2 was dissolved in dry diethyl ether (15 ml) under argon atmosphere. O-xylene (0.54 ml, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −50° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.68 mL, 1.0 eq) was added slowly maintaining the same temperature. The mixture was stirred until the reaction was complete. HBF4 solution (54%, 1.12 mL, 2 eq) was added and the resulting suspension was stirred for 30 minutes. The precipitate tetrafluoroborate salt was isolated by filtration, washed with diethyl ether at 0° C. and dried. The desired product was obtained as a slightly yellow oily solid (1.729 g). the mixture was cooled to a temperature below −50° C was added slowly maintaining the same temperature the resulting suspension was stirred for 30 minutes

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

Procedure: Fluoromethyl phenyl sulphide (85 g, 351.63 mmol) was added to a mixture of methanol (250 ml) and water (50 mL). The resulting mixture was cooled to a temperature between 0° C. and 5° C. NBS (75.10 g, 1.2 eq) was added in small portions maintaining the same temperature range. The reaction mixture was stirred until the reaction was complete, and then, was quenched with Na2SO3 solution (10%, 150 mL). The pH of the reaction mixture was adjusted to a value between 7 and 8 with NaHCO3 saturated solution. The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C. The residue was extracted with dichloromethane (200 mL, 300 mL). The combined organic layer was washed with water (2×300 mL) and concentrated to ⅓ of the volume. Heptane (50 mL) was added and the resulting mixture was concentrated again. The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70) to give 49.8 g (89.6%) of the desired product as colourless oil at rt, which is a white solid at −20° C. The resulting mixture was cooled to a temperature between 0° C. and 5° C maintaining the same temperature range was quenched with Na2SO3 solution (10%, 150 mL) The mixture was concentrated under vacuum at a temperature between 20° C. and 25° C The residue was extracted with dichloromethane (200 mL, 300 mL) The combined organic layer was washed with water (2×300 mL) concentrated Heptane (50 mL) was added the resulting mixture was concentrated again The crude product was purified by flash chromatography (Ethyl Acetate/Hexane 30:70)