6-氧代螺[2.5]辛烷-5-羧酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium (0.094 g, 4.08 mmol) was added to ethanol (15 ml) under stirring condition at room temperature. The resulting mixture was stirred for 30 min. To this freshly prepared clear solution of sodium ethoxide, were added ethyl 6-oxospiro[2.5]octane-5-carboxylate (0.4 g, 2.03 mmol) and 4-(4-(4-chlorophenyl) piperazin-1-yl)butanimidamide (0.343 g, 1.223 mmol) and the reaction mixture was heated at 85° C. for 18 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain crude residue which was dissolved with water (15 ml). Aqueous layer was extracted with ethylacetate (2×30 ml). The combined organic layer was dried over sodium sulphate, filtered and solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh) using 3-4% methanol in dichloromethane as eluent to obtain title compound (0.030 g, 4% yield). The resulting mixture was stirred for 30 min the reaction mixture was heated at 85° C. for 18 h The reaction mixture was cooled to room temperature concentrated under reduced pressure to obtain crude residue which Aqueous layer was extracted with ethylacetate (2×30 ml) The combined organic layer was dried over sodium sulphate filtered solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of spiro[2.5]octan-6-one (prepared according to the procedure reported in US2008176926) (0.900 g, 7.25 mmol) in dimethylformamide (10 ml) at 5° C. was added sodium hydride (0.580 g, 60%, 14.50 mmol) under a nitrogen atmosphere over a period of 10 min and the resulting mixture was stirred for an additional 20 min at the same temperature. To this reaction mixture, diethylcarbonate (1.72 g, 14.50 mmol) was added at 5° C. and stirred for 1 h and then allowed to stir at room temperature for 2 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to 0° C. and quenched with saturated ammonium chloride (10 ml) and diluted with water (30 ml). The resulting mixture was extracted with diethyl ether (2×20 ml), and the combined organic layer was washed with water (2×20 ml), dried over anhydrous sodium sulphate, filtered, and the solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh) using 1% ethyl acetate in hexane as eluent to yield the title compound (0.510 g, 35.9%). at 5° C. stirred for 1 h to stir at room temperature for 2 h quenched with saturated ammonium chloride (10 ml) diluted with water (30 ml) The resulting mixture was extracted with diethyl ether (2×20 ml) the combined organic layer was washed with water (2×20 ml) dried over anhydrous sodium sulphate filtered the solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh)