1,1-dioxothian-4-one

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

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

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

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 tetrahydrothiopyran-4-one (400 mg, 3.45 mmol) in acetonitrile (5 ml) was added aqueous Na2EDTA (3 ml, 0.0004 M). A mixture of oxone (6.30 g, 10.30 mmol) and sodium bicarbonate (2.70, 32 mmol) was added in small portions to the above solution over a period of 20 min. The slurry was stirred for another 1 h before being quenched with methylene chloride. The organic solvent was decanted and the solid residue was triturated with ethyl acetate (3×25 ml). The combined organic layers were dried over sodium sulfate and concentrated to give the desired ketone (0.37 g, 73%) as a colorless solid. mp 170-172° C. (lit. 168-170° C.); 1H NMR (500 MHz, CDCl3) 2.99 (t, J=6.8 Hz, 4H), 3.39 (t, J=6.8 Hz, 4H). Ref: Yang, D.; Yip, Y.-C.; Jiao, G.-S.; Wong, M.-K. Design of Efficient Ketone Catalysts for Epoxidation by Using the Field Effect. J. Org. Chem, 1998, 63, 8952-8956. was added in small portions to the above solution over a period of 20 min before being quenched with methylene chloride The organic solvent was decanted the solid residue was triturated with ethyl acetate (3×25 ml) The combined organic layers were dried over sodium sulfate concentrated

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

Procedure: To a solution of tetrahydrothiopyran-4-one (400 mg, 3.45 mmol) in acetonitrile (5 ml) was added aqueous Na2EDTA (3 ml, 0.0004 M). A mixture of oxone (6.30 g, 10.30 mmol) and sodium bicarbonate (2.70, 32 mmol) was added in small portions to the above solution over a period of 20 min. The slurry was stirred for another 1 h before being quenched with methylene chloride. The organic solvent was decanted and the solid residue was triturated with ethyl acetate (3×25 ml). The combined organic layers were dried over sodium sulfate and concentrated to give the desired ketone (0.37 g, 73%) as a colorless solid. mp 170-172° C. (lit. 168-170° C.); 1H NMR (500 MHz, CDCl3) 2.99 (t, J=6.8 Hz, 4H), 3.39 (t, J=6.8 Hz, 4H). Ref: Yang, D.; Yip, Y.-C.; Jiao, G.-S.; Wong, M.-K. Design of Efficient Ketone Catalysts for Epoxidation by Using the Field Effect. J. Org. Chem, 1998, 63, 8952-8956. was added in small portions to the above solution over a period of 20 min before being quenched with methylene chloride The organic solvent was decanted the solid residue was triturated with ethyl acetate (3×25 ml) The combined organic layers were dried over sodium sulfate concentrated

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

Procedure: To a solution of tetrahydrothiopyran-4-one (400 mg, 3.45 mmol) in acetonitrile (5 ml) was added aqueous Na2EDTA (3 ml, 0.0004 M). A mixture of oxone (6.30 g, 10.30 mmol) and sodium bicarbonate (2.70, 32 mmol) was added in small portions to the above solution over a period of 20 min. The slurry was stirred for another 1 h before being quenched with methylene chloride. The organic solvent was decanted and the solid residue was triturated with ethyl acetate (3×25 ml). The combined organic layers were dried over sodium sulfate and concentrated to give the desired ketone (0.37 g, 73%) as a colorless solid. mp 170-172° C. (lit. 168-170° C.); 1H NMR (500 MHz, CDCl3) 2.99 (t, J=6.8 Hz, 4H), 3.39 (t, J=6.8 Hz, 4H). Ref: Yang, D.; Yip, Y.-C.; Jiao, G.-S.; Wong, M.-K. Design of Efficient Ketone Catalysts for Epoxidation by Using the Field Effect. J. Org. Chem, 1998, 63, 8952-8956. was added in small portions to the above solution over a period of 20 min before being quenched with methylene chloride The organic solvent was decanted the solid residue was triturated with ethyl acetate (3×25 ml) The combined organic layers were dried over sodium sulfate concentrated

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

Procedure: To a solution of N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride (75 mg), tetrahydro-4H-thiopyran-4-one 1,1-dioxide (37.4 mg) and acetic acid (0.2 mL) in methanol (2 mL) was added 2-picoline-borane complex (38.2 mg). The mixture was stirred at room temperature overnight, and saturated aqueous sodium hydrogen carbonate solution was added under ice-cooling. The mixture was m extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol) and 10% hydrochloric acid methanol solution was added. The solvent was evaporated under reduced pressure. The residue was recrystallized from methanol/diisopropyl ether to give the title compound (32.0 mg). cooling extracted with ethyl acetate the extract was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol) and 10% hydrochloric acid methanol solution was added The solvent was evaporated under reduced pressure The residue was recrystallized from methanol/diisopropyl ether

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

Procedure: To a solution of N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride (75 mg), tetrahydro-4H-thiopyran-4-one 1,1-dioxide (37.4 mg) and acetic acid (0.2 mL) in methanol (2 mL) was added 2-picoline-borane complex (38.2 mg). The mixture was stirred at room temperature overnight, and saturated aqueous sodium hydrogen carbonate solution was added under ice-cooling. The mixture was m extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol) and 10% hydrochloric acid methanol solution was added. The solvent was evaporated under reduced pressure. The residue was recrystallized from methanol/diisopropyl ether to give the title compound (32.0 mg). cooling extracted with ethyl acetate the extract was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol) and 10% hydrochloric acid methanol solution was added The solvent was evaporated under reduced pressure The residue was recrystallized from methanol/diisopropyl ether

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

Procedure: Potassium tert-butoxide (3.5 mL, 3.5 mmol, 1.0 M in THF) was stirred at 0° C. and THF (8 mL) was added. Diethyl (cyanomethyl)phosphonate (0.56 mL, 3.5 mmol) was added slowly by syringe. The reaction mixture was maintained at 0° C. for 10 minutes, then warmed to ambient temperature and maintained for 1 hour. The mixture was cooled to 0° C. and treated with the dropwise addition of dihydro-2H-thiopyran-4(3H)-one 1,1-dioxide (0.50 g, 3.4 mmol) in THF (5 mL). After addition, the mixture was maintained at 0° C. for 20 minutes, then warmed to ambient temperature and maintained for 18 hours. The reaction mixture was then diluted with water and extracted with EtOAc. The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified MPLC on silica gel (using a gradient elution of 0-50% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to the title compound. warmed to ambient temperature maintained for 1 hour The mixture was cooled to 0° C. After addition the mixture was maintained at 0° C. for 20 minutes warmed to ambient temperature maintained for 18 hours extracted with EtOAc The combined organic extracts were washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified MPLC on silica gel ( a gradient elution of 0-50% EtOAc/hexanes) concentrated in vacuo to the title compound

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

Procedure: Potassium tert-butoxide (3.5 mL, 3.5 mmol, 1.0 M in THF) was stirred at 0° C. and THF (8 mL) was added. Diethyl (cyanomethyl)phosphonate (0.56 mL, 3.5 mmol) was added slowly by syringe. The reaction mixture was maintained at 0° C. for 10 minutes, then warmed to ambient temperature and maintained for 1 hour. The mixture was cooled to 0° C. and treated with the dropwise addition of dihydro-2H-thiopyran-4(3H)-one 1,1-dioxide (0.50 g, 3.4 mmol) in THF (5 mL). After addition, the mixture was maintained at 0° C. for 20 minutes, then warmed to ambient temperature and maintained for 18 hours. The reaction mixture was then diluted with water and extracted with EtOAc. The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified MPLC on silica gel (using a gradient elution of 0-50% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to the title compound. warmed to ambient temperature maintained for 1 hour The mixture was cooled to 0° C. After addition the mixture was maintained at 0° C. for 20 minutes warmed to ambient temperature maintained for 18 hours extracted with EtOAc The combined organic extracts were washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified MPLC on silica gel ( a gradient elution of 0-50% EtOAc/hexanes) concentrated in vacuo to the title compound

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

Procedure: To 1,1-dioxo-tetrahydrothiopyran-4-one (6.3 g, 36 mmol) in H2O (55 mL) was added, in portions, sodium borohydride (720 mg, 18.9 mmol). The reaction mixture was stirred at room temperature for 30 minutes and then the pH was adjusted to 4 with aq. HCl. The reaction mixture was concentrated and suspended in acetone and filtered. The filtrate was concentrated and triturated with ether/hexane to provide 1,1-dioxo-tetrahydrothiopyran-4-ol (5.63 g, 90%) as a white solid. The reaction mixture was concentrated filtered The filtrate was concentrated triturated with ether/hexane