ethyl 2-(azetidin-3-yl)acetate

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

実験手順: Under nitrogen atmosphere, 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (400 mg, 1.40 mmol) was dissolved in methylene chloride (15 ml), then diisopropylethylamine (537 μl, 3.08 mmol) and ethyl azetidine-3-acetate (503 mg, 2.80 mmol) dissolved in methylene chloride (5 ml) were added, followed by heating under reflux for 19 hours. After cooling, diluting with chloroform and washing with water, the organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography. From the eluate with ethyl acetate/hexane (1:1, v/v), the entitled compound (420 mg, 76%) was obtained as a colorless oil. were added by heating under reflux for 19 hours After cooling washing with water the organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure

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

実験手順: Under nitrogen atmosphere, 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (400 mg, 1.40 mmol) was dissolved in methylene chloride (15 ml), then diisopropylethylamine (537 μl, 3.08 mmol) and ethyl azetidine-3-acetate (503 mg, 2.80 mmol) dissolved in methylene chloride (5 ml) were added, followed by heating under reflux for 19 hours. After cooling, diluting with chloroform and washing with water, the organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography. From the eluate with ethyl acetate/hexane (1:1, v/v), the entitled compound (420 mg, 76%) was obtained as a colorless oil. were added by heating under reflux for 19 hours After cooling washing with water the organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated away 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 stirring mixture of azetidin-3-yl-acetic acid ethyl ester (1.0 g, 6.98 mmol), in saturated aqueous sodium bicarbonate (5 mL) and THF (5 mL) at 0° C. was added carbobenzyloxy chloride (1.1 mL, 7.68 mmol) dropwise. The ice bath was removed and the reaction mixture was stirred at room temperature for 2 hrs, then extracted with ethyl acetate acetate (3×20 mL). The combined ethyl acetate layer was washed with water (10 mL), brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel, eluting with 20% ethyl acetate in hexane to give 0.30 g of the title compound. The ice bath was removed extracted with ethyl acetate acetate (3×20 mL) The combined ethyl acetate layer was washed with water (10 mL), brine (10 mL) dried over anhydrous sodium sulfate filtered concentrated The residue was chromatographed on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: To a solution of (1-benzhydrylazetidin-3-ylidene)-acetic acid ethyl ester (5.0 g, 16 mmol) in ethanol (200 mL) was added palladium hydroxide on carbon (1.5 g). This mixture was vigorously shaken under a 50 psi hydrogen atmosphere for 24 hrs, then filtered and concentrated to give an oil, used without additional purification. filtered concentrated to give an oil used without additional purification

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

実験手順: Under nitrogen atmosphere, 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (400 mg, 1.40 mmol) was dissolved in methylene chloride (15 ml), then diisopropylethylamine (537 μl, 3.08 mmol) and ethyl azetidine-3-acetate (503 mg, 2.80 mmol) dissolved in methylene chloride (5 ml) were added, followed by heating under reflux for 19 hours. After cooling, diluting with chloroform and washing with water, the organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography. From the eluate with ethyl acetate/hexane (1:1, v/v), the entitled compound (420 mg, 76%) was obtained as a colorless oil. were added by heating under reflux for 19 hours After cooling washing with water the organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated away under reduced pressure