thietan-3-ol

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

Procedure: A solution of triphenylphosphine (0.79 g) in THF (22 ml) was cooled under argon to −10° C. Diethylazodicarboxylate (DEAD, 1.57 g) was added dropwise then thietan-3-ol (0.4 g) and (3-oxo-isoxazolidin-4-yl)-carbamic acid tert-butyl ester (0.27 g, prepared from (D)-cycloserine as described in Chem. Pharm. Bull. 2002, 50(4) 554-557). The reaction mixture was stirred at room temperature for 24 hours then the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent cyclohexane/ethyl acetate) to afford the title product as a white solid (51 mg). 1H-NMR (CDCl3, 400 MHz): 5.45 (q, 1H), 5.05 (m, 1H), 4.90 (m, 1H), 4.50 (t, 1H), 4.10 (dd, 1H), 3.55 (m, 2H), 3.40 (m, 2H), 1.50 (s, 9H). the solvent was removed in vacuo The crude product was purified by column chromatography (eluent cyclohexane/ethyl acetate)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl azodicarboxylate (4.3 g) was added all at once to a stirred mixture of 3-thietanol (2.0 g), N-hydroxyphthalimide (3.6 g) and triphenylphosphine (5.8 g) in dry tetrahydrofuran (100 ml) at room temperature. The temperature of the reaction mixture was raised to 40° C. The mixture became clear solution and was stirred for 12 hours at room temperature. Tetrahydrofuran was evaporated in vacuo and the residue was dissolved in ethyl acetate (50 ml). The insoluble substance was filtered off. The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) and with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate and evaporated. The residue was dissolved in methylene chloride (50 ml), subjected to column chromatography on silica gel and eluted with methylene chloride. The fractions containing the object compound were collected and evaporated in vacuo to give N-(3-thietanyloxy)phthalimide (2.0 g). Tetrahydrofuran was evaporated in vacuo the residue was dissolved in ethyl acetate (50 ml) The insoluble substance was filtered off The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate evaporated The residue was dissolved in methylene chloride (50 ml) eluted with methylene chloride The fractions containing the object compound were collected evaporated in vacuo

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl azodicarboxylate (4.3 g) was added all at once to a stirred mixture of 3-thietanol (2.0 g), N-hydroxyphthalimide (3.6 g) and triphenylphosphine (5.8 g) in dry tetrahydrofuran (100 ml) at room temperature. The temperature of the reaction mixture was raised to 40° C. The mixture became clear solution and was stirred for 12 hours at room temperature. Tetrahydrofuran was evaporated in vacuo and the residue was dissolved in ethyl acetate (50 ml). The insoluble substance was filtered off. The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) and with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate and evaporated. The residue was dissolved in methylene chloride (50 ml), subjected to column chromatography on silica gel and eluted with methylene chloride. The fractions containing the object compound were collected and evaporated in vacuo to give N-(3-thietanyloxy)phthalimide (2.0 g). Tetrahydrofuran was evaporated in vacuo the residue was dissolved in ethyl acetate (50 ml) The insoluble substance was filtered off The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate evaporated The residue was dissolved in methylene chloride (50 ml) eluted with methylene chloride The fractions containing the object compound were collected evaporated in vacuo

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl azodicarboxylate (4.3 g) was added all at once to a stirred mixture of 3-thietanol (2.0 g), N-hydroxyphthalimide (3.6 g) and triphenylphosphine (5.8 g) in dry tetrahydrofuran (100 ml) at room temperature. The temperature of the reaction mixture was raised to 40° C. The mixture became clear solution and was stirred for 12 hours at room temperature. Tetrahydrofuran was evaporated in vacuo and the residue was dissolved in ethyl acetate (50 ml). The insoluble substance was filtered off. The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) and with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate and evaporated. The residue was dissolved in methylene chloride (50 ml), subjected to column chromatography on silica gel and eluted with methylene chloride. The fractions containing the object compound were collected and evaporated in vacuo to give N-(3-thietanyloxy)phthalimide (2.0 g). Tetrahydrofuran was evaporated in vacuo the residue was dissolved in ethyl acetate (50 ml) The insoluble substance was filtered off The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate evaporated The residue was dissolved in methylene chloride (50 ml) eluted with methylene chloride The fractions containing the object compound were collected evaporated in vacuo

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

Procedure: A solution of thietan-3-ol (450 mg) and Et3N (1.3 ml) in chloroform (5 ml) was added dropwise to over 30 minutes to a solution of p-toluenesulfonic anhydride (1.63 g) in dichloromethane (10 ml) at −20° C. under argon atmosphere. After 2 hours, pyridine (0.8 ml) was added and the resulting mixture was stirred at room temperature for 2 days. The precipitated solid was collected by filtration (300 mg). 1H-NMR (DMSO, 400 MHz): 2.30 (s, 3H), 3.57 (t, 2H), 4.09 (t, 2H), 6.16 (q, 1H), 7.12 (d, 2H), 7.50 (d, 2H), 8.20 (t, 2H), 8.66 (t, 1H), 9.21 (d, 1H). The precipitated solid was collected by filtration (300 mg)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of thietan-3-ol (450 mg) and Et3N (1 ml) in dichloromethane (3 ml) was added dropwise to over 30 minutes to a solution of p-toluenesulfonyl chloride (1 g) in dichloromethane (3 ml) at −10° C. under argon atmosphere. The yellow solution was stirred at −10° C. for 1 hour then pyridine (1 ml) was added, and the resulting red solution was stirred for 1 hour at −10° C. The precipitated solid was collected by filtration then washed with diethyl ether (3×5 ml) and dried under high vacuum to afford the title compound as a white solid (405 mg). MS (Method A) positive ion mass: 152 (3-pyridinium thietane), negative ion mass: 171 (p-toluenesulfonate). 1H-NMR (DMSO, 400 MHz): 2.30 (s, 3H), 3.57 (t, 2H), 4.09 (t, 2H), 6.16 (q, 1H), 7.12 (d, 2H), 7.50 (d, 2H), 8.20 (t, 2H), 8.66 (t, 1H), 9.21 (d, 1H). the resulting red solution was stirred for 1 hour at −10° C The precipitated solid was collected by filtration then washed with diethyl ether (3×5 ml) dried under high vacuum

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

Procedure: 22.99 g of methacryloyl chloride (0.22 mole) are slowly poured (20 mins), with stirring, into a solution of 18 g of 3-thietanol (0.2 mole) in dimethylaniline (80 g, i.e. 0.66 mole). Stirring is then continued at ambient temperature for 8 days. After this time, the reaction mixture is poured on to the following mixture: 270 g of ice-27 cm3 (47.5 g) of concentrated sulphuric acid. The solution is stirred for 2 hours, then theorganic phase is extracted with ether. It is then washed with demineralisedwater until neutral and dried over sodium sulphate. The ether is eliminatedand then the remaining product is distilled in the presence of hydroquinone. The distillation temperature is 44° C. under a pressure of 0.1 mm of Hg. 8.5 g of 3-thietanyl methacrylate are obtained. After this time, the reaction mixture is poured on to the following mixture The solution is stirred for 2 hours theorganic phase is extracted with ether It is then washed with demineralisedwater until neutral and dried over sodium sulphate the remaining product is distilled in the presence of hydroquinone is 44° C. under a pressure of 0.1 mm of Hg

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

Procedure: A solution of triphenylphosphine (0.79 g) in THF (22 ml) was cooled under argon to −10° C. Diethylazodicarboxylate (DEAD, 1.57 g) was added dropwise then thietan-3-ol (0.4 g) and (3-oxo-isoxazolidin-4-yl)-carbamic acid tert-butyl ester (0.27 g, prepared from (D)-cycloserine as described in Chem. Pharm. Bull. 2002, 50(4) 554-557). The reaction mixture was stirred at room temperature for 24 hours then the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent cyclohexane/ethyl acetate) to afford the title product as a white solid (51 mg). 1H-NMR (CDCl3, 400 MHz): 5.45 (q, 1H), 5.05 (m, 1H), 4.90 (m, 1H), 4.50 (t, 1H), 4.10 (dd, 1H), 3.55 (m, 2H), 3.40 (m, 2H), 1.50 (s, 9H). the solvent was removed in vacuo The crude product was purified by column chromatography (eluent cyclohexane/ethyl acetate)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl azodicarboxylate (4.3 g) was added all at once to a stirred mixture of 3-thietanol (2.0 g), N-hydroxyphthalimide (3.6 g) and triphenylphosphine (5.8 g) in dry tetrahydrofuran (100 ml) at room temperature. The temperature of the reaction mixture was raised to 40° C. The mixture became clear solution and was stirred for 12 hours at room temperature. Tetrahydrofuran was evaporated in vacuo and the residue was dissolved in ethyl acetate (50 ml). The insoluble substance was filtered off. The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) and with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate and evaporated. The residue was dissolved in methylene chloride (50 ml), subjected to column chromatography on silica gel and eluted with methylene chloride. The fractions containing the object compound were collected and evaporated in vacuo to give N-(3-thietanyloxy)phthalimide (2.0 g). Tetrahydrofuran was evaporated in vacuo the residue was dissolved in ethyl acetate (50 ml) The insoluble substance was filtered off The filtrate was washed three times with a saturated aqueous solution of sodium bicarbonate (50 ml) with a saturated aqueous solution of sodium chloride (50 ml), dried over magnesium sulfate evaporated The residue was dissolved in methylene chloride (50 ml) eluted with methylene chloride The fractions containing the object compound were collected evaporated in vacuo