2-methyl-4,5-dihydro-1,3-thiazole

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methylthiazoline (10.1 g) in dioxane (20 ml) was added 2-bromoethanol (13.8 g), and the mixture was heated under reflux for about 6 hours. After cooling the reaction, acetone (30 ml) and ether (130 ml) were added with stirring, and the resulting mixture was left standing. After the pale brown supernatant was discarded, ether (150 ml) was further added to the amorphous precipitate thus obtained. The mixture was stirred and left standing. Supernatant obtained was discarded, and the viscous precipitates obtained was left standing at an ambient temperature under reduced pressure to give the title compound as the yellow amorphous residue. the mixture was heated under reflux for about 6 hours After cooling were added the resulting mixture was left thus obtained The mixture was stirred left Supernatant obtained the viscous precipitates obtained was left standing at an ambient temperature under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-thiazoline (1.01 g) in dry tetrahydrofuran at −70° C. was added a solution of n-butyl lithium in hexanes (2.5M, 4.0 ml) dropwise over 10 min. After stirring at −70° C. for 2 h, 1,7-dibromoheptane (12.9 g) was added in one portion (temperature increased to −45° C.). The mixture was cooled again to −70° C. for 1 h and then allowed to warm to room temperature over 1 h. The mixture was cooled to 0° C. and water (10 ml) added, followed by dilute hydrochloric acid (to pH 2). The organic layer was separated and the aqueous layer extracted with diethyl ethyl (2×20 ml). The organic layers were combined and washed with water and brine and dried over magnesium sulfate. Evaporation under reduced pressure gave an oil that was chromatographed on silica gel using 40-60° C. petroleum ether:ethyl acetate 5:1 to give 1-bromo-8-(2-thiazolinyl)octane (1.06 g). 1H-NMR (CDCl3) δ 1.2-1.5 (6H, m), 1.5-1.75 (4H, m), 1.75-1.95 (2H, m), 2.50 (2H, t), 3.28 (2H, t), 3.40 (2H, t) and 4.21 (2H, dt). The mixture was cooled again to −70° C. for 1 h to warm to room temperature over 1 h The mixture was cooled to 0° C. The organic layer was separated the aqueous layer extracted with diethyl ethyl (2×20 ml) washed with water and brine dried over magnesium sulfate Evaporation under reduced pressure gave an oil that was chromatographed on silica gel using 40-60° C. petroleum ether:ethyl acetate 5:1

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-thiazoline (1.01 g) in dry tetrahydrofuran at −70° C. was added a solution of n-butyl lithium in hexanes (2.5M, 4.0 ml) dropwise over 10 min. After stirring at −70° C. for 2 h, 1,7-dibromoheptane (12.9 g) was added in one portion (temperature increased to −45° C.). The mixture was cooled again to −70° C. for 1 h and then allowed to warm to room temperature over 1 h. The mixture was cooled to 0° C. and water (10 ml) added, followed by dilute hydrochloric acid (to pH 2). The organic layer was separated and the aqueous layer extracted with diethyl ethyl (2×20 ml). The organic layers were combined and washed with water and brine and dried over magnesium sulfate. Evaporation under reduced pressure gave an oil that was chromatographed on silica gel using 40-60° C. petroleum ether:ethyl acetate 5:1 to give 1-bromo-8-(2-thiazolinyl)octane (1.06 g). 1H-NMR (CDCl3) δ 1.2-1.5 (6H, m), 1.5-1.75 (4H, m), 1.75-1.95 (2H, m), 2.50 (2H, t), 3.28 (2H, t), 3.40 (2H, t) and 4.21 (2H, dt). The mixture was cooled again to −70° C. for 1 h to warm to room temperature over 1 h The mixture was cooled to 0° C. The organic layer was separated the aqueous layer extracted with diethyl ethyl (2×20 ml) washed with water and brine dried over magnesium sulfate Evaporation under reduced pressure gave an oil that was chromatographed on silica gel using 40-60° C. petroleum ether:ethyl acetate 5:1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 109 mg of 3-hydroxyazetidine.HCl [Compound (1)] in 5 ml of ethanol was added a mixture of 133 mg of 2-methylthiazoline [Compound (2)] and sodium methoxide, and the reaction mixture was refluxed for 8 hours. After removal of the solvent under reduced pressure, the resulting residue was dissolved in chloroform and washed with 50% aqueous potassium carbonate solution. The solvent was removed under reduced pressure to give 119 mg (81.5%) of 3-hydroxy-1-(thiazolin-2-yl)azetidine [Compound (3)] as a crystaline. the reaction mixture was refluxed for 8 hours After removal of the solvent under reduced pressure the resulting residue was dissolved in chloroform washed with 50% aqueous potassium carbonate solution The solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methylthiazoline (10.1 g) in dioxane (20 ml) was added 2-bromoethanol (13.8 g), and the mixture was heated under reflux for about 6 hours. After cooling the reaction, acetone (30 ml) and ether (130 ml) were added with stirring, and the resulting mixture was left standing. After the pale brown supernatant was discarded, ether (150 ml) was further added to the amorphous precipitate thus obtained. The mixture was stirred and left standing. Supernatant obtained was discarded, and the viscous precipitates obtained was left standing at an ambient temperature under reduced pressure to give the title compound as the yellow amorphous residue. the mixture was heated under reflux for about 6 hours After cooling were added the resulting mixture was left thus obtained The mixture was stirred left Supernatant obtained the viscous precipitates obtained was left standing at an ambient temperature under reduced pressure