tert-butyl 1,1-dioxo-1,4-thiazinane-4-carboxylate

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

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

Procedure: A solution of N—BOC-1,1-dioxothiomorpholine (85 mg, 0.365 mmol) in a mixture of DCM (1 mL) and TFA (1 mL) was stirred at room temperature for 0.1 h before concentrating under vacuum and drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h. The salt was dissolved in dry DMF (1 mL) and reacted with Example 22a (92 mg, 0.18 mmol) and K2CO3 (2.16 eq.) under General Procedure L. The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19) to afford 23 (14 mg, 14%) and 24 (13 mg, 13%) as clear colourless oils. before concentrating under vacuum drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h The salt was dissolved in dry DMF (1 mL) The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19)

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

Procedure: A solution of N—BOC-1,1-dioxothiomorpholine (85 mg, 0.365 mmol) in a mixture of DCM (1 mL) and TFA (1 mL) was stirred at room temperature for 0.1 h before concentrating under vacuum and drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h. The salt was dissolved in dry DMF (1 mL) and reacted with Example 22a (92 mg, 0.18 mmol) and K2CO3 (2.16 eq.) under General Procedure L. The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19) to afford 23 (14 mg, 14%) and 24 (13 mg, 13%) as clear colourless oils. before concentrating under vacuum drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h The salt was dissolved in dry DMF (1 mL) The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19)

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

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

Procedure: tert-Butyl 1,1-dioxothiomorpholine-4-carboxylate (2.03 g, 8.63 mmol) was dissolved in a mixture of hydrochloric acid-methanol 10 (20 ml, purchased from Tokyo Kasei Kogyo Co., Ltd) and tetrahydrofuran (20 ml); hydrochloric acid (4.0 ml) was added thereto during stirring at room temperature; and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated; methanol (20 ml), tetrahydrofuran (20 ml) and hydrochloric acid (4.0 ml) were added to the obtained crystals. Furthermore, water (10 ml) was added to this solution to perfectly dissolve the crystals; and this solution was stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure; and the obtained crystals were suspended in methanol, filtered off, washed with methanol, and dried under aeration to yield the title compound as colorless crystals (1.49 g, 8.65 mmol, quantitative). and the reaction mixture was stirred at room temperature for 3 hours The reaction mixture was concentrated methanol (20 ml), tetrahydrofuran (20 ml) and hydrochloric acid (4.0 ml) were added to the obtained crystals Furthermore, water (10 ml) was added to this solution to perfectly dissolve the crystals and this solution was stirred at room temperature for 1 hour The solvent was concentrated under reduced pressure filtered off washed with methanol dried under aeration

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

Procedure: tert-Butyl thiomorpholine-4-carboxylate (1.91 g, 9.42 mmol) was dissolved in dichloromethane (50 ml); m-chloroperbenzoic acid (5.0 g, 19 mmol) was gradually added while cooled with ice bath, stirred, and under nitrogen atmosphere; and the reaction mixture was stirred at room temperature for 12 hours. After addition of a saturated aqueous solution of sodium thiosulfate, the reaction mixture was kept stirred for a while; and this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Triethylamine (8.1 ml, 58 mmol) were added to the obtained crystals; and the reaction mixture was stirred at room temperature. tert-Butoxycarbonyl dicarbonate (13.3 ml, 58 mmol) was added thereto; and the reaction mixture was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure; and the obtained crystals were suspended with a solvent mixture of diethyl ether:ethanol=10:1, filtered off, washed with diethyl ether and dried under aeration to yield the title compound as colorless crystals (2.03 g, 8.63 mmol, 91.6%). while cooled with ice bath and the reaction mixture was stirred at room temperature for 12 hours the reaction mixture was kept stirred for a while and this was subjected to extraction with ethyl acetate washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure and the reaction mixture was stirred at room temperature and the reaction mixture was stirred at room temperature for 10 hours The reaction mixture was concentrated under reduced pressure and the obtained crystals were suspended with a solvent mixture of diethyl ether ethanol=10:1, filtered off washed with diethyl ether dried under aeration

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

Procedure: tert-Butyl 1,1-dioxothiomorpholine-4-carboxylate (2.03 g, 8.63 mmol) was dissolved in a mixture of hydrochloric acid-methanol 10 (20 ml) and tetrahydrofuran (20 ml); hydrochloric acid (4.0 ml) was added thereto during stirring at room temperature; and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated; methanol (20 ml), tetrahydrofuran (20 ml) and hydrochloric acid (4.0 ml) were added to the obtained crystals. Furthermore, water (10 ml) was added to this solution to perfectly dissolve the crystals; and this solution was stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure; and the obtained crystals were suspended in methanol, filtered off, washed with methanol, and dried under aeration to yield the title compound as colorless crystals (1.49 g, 8.65 mmol, quantitative). and the reaction mixture was stirred at room temperature for 3 hours The reaction mixture was concentrated methanol (20 ml), tetrahydrofuran (20 ml) and hydrochloric acid (4.0 ml) were added to the obtained crystals Furthermore, water (10 ml) was added to this solution to perfectly dissolve the crystals and this solution was stirred at room temperature for 1 hour The solvent was concentrated under reduced pressure filtered off washed with methanol dried under aeration

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

Procedure: tert-Butyl thiomorpholine-4-carboxylate (1.91 g, 9.42 mol) was dissolved in dichloromethane (50 ml); m-chloroperbenzoic acid (5.0 g, 19 mmol) was gradually added while cooled with ice bath, stirred, and under nitrogen atmosphere; and the reaction mixture was stirred at room temperature for 12 hours. After addition of a saturated aqueous solution of sodium thiosulfate, the reaction mixture was kept stirred for a while; and this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Triethylamine (8.1 ml, 58 ml) were added to the obtained crystals; and the reaction mixture was stirred at room temperature. tert-Butoxycarbonyl dicarbonate (13.3 ml, 58 mmol) was added thereto; and the reaction mixture was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure; and the obtained crystals were suspended with a solvent mixture of diethyl ether:ethanol=10:1, filtered off, washed with diethyl ether and dried under aeration to yield the title compound as colorless crystals (2.03 g, 8.63 mmol, 91.6%). while cooled with ice bath and the reaction mixture was stirred at room temperature for 12 hours the reaction mixture was kept stirred for a while and this was subjected to extraction with ethyl acetate washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure Triethylamine (8.1 ml, 58 ml) were added to the obtained crystals and the reaction mixture was stirred at room temperature and the reaction mixture was stirred at room temperature for 10 hours The reaction mixture was concentrated under reduced pressure and the obtained crystals were suspended with a solvent mixture of diethyl ether ethanol=10:1, filtered off washed with diethyl ether dried under aeration

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

Procedure: A solution of N—BOC-1,1-dioxothiomorpholine (85 mg, 0.365 mmol) in a mixture of DCM (1 mL) and TFA (1 mL) was stirred at room temperature for 0.1 h before concentrating under vacuum and drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h. The salt was dissolved in dry DMF (1 mL) and reacted with Example 22a (92 mg, 0.18 mmol) and K2CO3 (2.16 eq.) under General Procedure L. The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19) to afford 23 (14 mg, 14%) and 24 (13 mg, 13%) as clear colourless oils. before concentrating under vacuum drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h The salt was dissolved in dry DMF (1 mL) The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19)