3-bromo-4-fluorobenzenethiol

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

Procedure: 3-Bromo-4-fluorobenzenethiol (2.071 g, 10 mmol) in dimethylformamide (10 mL) was treated with 60% sodium hydride (0.480 g, 12.00 mmol). The solution was stirred for 10 minutes at room temperature. Trifluoroiodomethane (2.74 g, 14.00 mmol) was released into a balloon with a three-way stopcock. The balloon was then put onto the flask and trifluoroiodomethane was released into the reaction. After 1 hour, all the content in the balloon was gone. And the balloon was filled with 2.74 g of trifluoroiodomethane again. The reaction mixture was stirred for 16 hours. The reaction mixture was poured into water, and extracted with ethyl acetate several times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting oil was used directly in the next reaction. was released into the reaction After 1 hour The reaction mixture was stirred for 16 hours extracted with ethyl acetate several times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated The resulting oil was used directly in the next reaction

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-fluorobenzenethiol (3.89 g, 18.79 mmol) and sodium hydroxide (3.95 mL, 19.73 mmol) in MeOH was stirred at 0° C. for 10 minutes. To this solution was added iodoethane (1.803 mL, 22.54 mmol). The reaction mixture was stirred at ambient temperature for 6 hours. The solvent was removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with addition ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (4.35 g, 18.50 mmol, 98% yield). It was used directly for the next reaction. The reaction mixture was stirred at ambient temperature for 6 hours The solvent was removed the residue was partitioned between water and ethyl acetate The aqueous layer was extracted with addition ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-fluorobenzenethiol (3.89 g, 18.79 mmol) and sodium hydroxide (3.95 mL, 19.73 mmol) in MeOH was stirred at 0° C. for 10 minutes. To this solution was added iodoethane (1.803 mL, 22.54 mmol). The reaction mixture was stirred at ambient temperature for 6 hours. The solvent was removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with addition ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (4.35 g, 18.50 mmol, 98% yield). It was used directly for the next reaction. The reaction mixture was stirred at ambient temperature for 6 hours The solvent was removed the residue was partitioned between water and ethyl acetate The aqueous layer was extracted with addition ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated

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

Procedure: To a mixture of 3-bromo-4-fluorobenzenethiol (2.07 g, 10 mmol) and K2CO3 (4.14 g, 30 mmol) in acetone (20 mL) was added EtI (3.12 g, 20 mmol). The mixture was stirred at room temperature for 12 h, filtered, and the volatile components were removed under vacuum to give the title compound (2.34 g) as light yellow oil which was carried on without purification. 1H NMR (CDCl3, 400 MHz): d 7.54 (dd, J1=6.4 Hz, J2=2.4 Hz, 1H), 7.26-7.25 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 2.91 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H). filtered the volatile components were removed under vacuum

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

Procedure: To a mixture of 3-bromo-4-fluorobenzenethiol (2.07 g, 10 mmol) and K2CO3 (4.14 g, 30 mmol) in acetone (20 mL) was added EtI (3.12 g, 20 mmol). The mixture was stirred at room temperature for 12 h, filtered, and the volatile components were removed under vacuum to give the title compound (2.34 g) as light yellow oil which was carried on without purification. 1H NMR (CDCl3, 400 MHz): d 7.54 (dd, J1=6.4 Hz, J2=2.4 Hz, 1H), 7.26-7.25 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 2.91 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H). filtered the volatile components were removed under vacuum

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

Procedure: Using analogous reagents and reaction conditions as described in Example 24 for the preparation of I-24a above, 3-bromo-4-fluoro-benzenethiol (2.0 g, 9.756 mmol) was reacted with 1-chloro-propan-2-one (0.86 mL, 10.73 mmol), DMF (6.0 mL), and potassium carbonate (2.69 g, 19.51 mmol) to afford crude product which was purified by column on silica gel (5% ethyl acetate in hexane) to afford 2.1 g of the product (82% yield). reagents and reaction conditions to afford crude product which was purified by column on silica gel (5% ethyl acetate in hexane)

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

Procedure: Using analogous reagents and reaction conditions as described in Example 24 for the preparation of I-24a above, 3-bromo-4-fluoro-benzenethiol (2.0 g, 9.756 mmol) was reacted with 1-chloro-propan-2-one (0.86 mL, 10.73 mmol), DMF (6.0 mL), and potassium carbonate (2.69 g, 19.51 mmol) to afford crude product which was purified by column on silica gel (5% ethyl acetate in hexane) to afford 2.1 g of the product (82% yield). reagents and reaction conditions to afford crude product which was purified by column on silica gel (5% ethyl acetate in hexane)

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

Procedure: To a mixture of 3-bromo-4-fluorobenzenethiol (2.07 g, 10 mmol) and K2CO3 (4.14 g, 30 mmol) in acetone (20 mL) was added EtI (3.12 g, 20 mmol). The mixture was stirred at room temperature for 12 h, filtered, and the volatile components were removed under vacuum to give the title compound (2.34 g) as light yellow oil which was carried on without purification. 1H NMR (CDCl3, 400 MHz): δ 7.54 (dd, J1=6.4 Hz, J2=2.4 Hz, 1H), 7.26-7.25 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 2.91 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H). filtered the volatile components were removed under vacuum

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

Procedure: To a mixture of 3-bromo-4-fluorobenzenethiol (2.07 g, 10 mmol) and K2CO3 (4.14 g, 30 mmol) in acetone (20 mL) was added EtI (3.12 g, 20 mmol). The mixture was stirred at room temperature for 12 h, filtered, and the volatile components were removed under vacuum to give the title compound (2.34 g) as light yellow oil which was carried on without purification. 1H NMR (CDCl3, 400 MHz): δ 7.54 (dd, J1=6.4 Hz, J2=2.4 Hz, 1H), 7.26-7.25 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 2.91 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H). filtered the volatile components were removed under vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-fluorobenzenethiol (3.89 g, 18.8 mmol) and 5M sodium hydroxide (3.95 mL, 19.7 mmol) in methanol (40 mL) was stirred at 0° C. for 10 minutes. To this solution was added iodoethane (1.803 mL, 22.54 mmol). The reaction mixture was stirred at ambient temperature for 6 hours. The solvent was removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with addition ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (4.35 g, 98%). It was used directly for the next reaction. The reaction mixture was stirred at ambient temperature for 6 hours The solvent was removed the residue was partitioned between water and ethyl acetate The aqueous layer was extracted with addition ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated

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

Procedure: 3-Bromo-4-fluorobenzenethiol (2.071 g, 10 mmol) in dimethylformamide (10 mL) was treated with 60% sodium hydride (0.480 g, 12.00 mmol). The solution was stirred for 10 minutes at room temperature. Trifluoroiodomethane (2.74 g, 14.00 mmol) was released into a balloon with a three-way stopcock. The balloon was then put onto the flask and trifluoroiodomethane was released into the reaction. After 1 hour, all the content in the balloon was gone. And the balloon was filled with 2.74 g of trifluoroiodomethane again. The reaction mixture was stirred for 16 hours. The reaction mixture was poured into water, and extracted with ethyl acetate several times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting oil was used directly in the next reaction. was released into the reaction After 1 hour The reaction mixture was stirred for 16 hours extracted with ethyl acetate several times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated The resulting oil was used directly in the next reaction

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-fluorobenzenethiol (3.89 g, 18.79 mmol) and sodium hydroxide (3.95 mL, 19.73 mmol) in MeOH was stirred at 0° C. for 10 minutes. To this solution was added iodoethane (1.803 mL, 22.54 mmol). The reaction mixture was stirred at ambient temperature for 6 hours. The solvent was removed, and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with addition ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (4.35 g, 18.50 mmol, 98% yield). It was used directly for the next reaction. The reaction mixture was stirred at ambient temperature for 6 hours The solvent was removed the residue was partitioned between water and ethyl acetate The aqueous layer was extracted with addition ethyl acetate three times The combined organic layers were washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate filtered concentrated