cis-5-Oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylic acid tert-butyl ester

(0551) (Cis)-hexahydrocyclopenta[c]pyrrol-5(1H)-one (2.0 g, 16 mmol) was dissolved in dichloromethane (50 mL), and di-tert-butyl dicarbonate (5.2 g, 24 mmol), triethylamine (3.2 g, 32 mmol) and 4-dimethylaminopyridine (195 mg, 1.6 mmol) were added. The mixture was reacted at room temperature under stirring for 16 h. After the reaction, water (100 mL) was added, and the water phase and the organic phase were separated. The organic phase was dried with anhydrous sodium sulfate, filtrated, and concentrated to get the crude product. The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=10:1) to get the title compound (3.4 g, yield: 94.4percent).Step 3tert-butyl(cis)-5-oxo-1, 3, 3a, 4, 6, 6a-hexahydrocyclopenta[c]pyrrole-2-carboxylatetert-butyl N-allyl-N-prop-2-yne-carbamate 5c (16.70 g, 0.86 mol) was dissolved in 100 mL of dichloromethane followed by the addition of dicobalt octacarbonyl (29.40 g, 0.86 mol) and 31 mL of water. The resulting solution was heated to reflux and stirred for 3 hours, added with 10 mL of water. The reaction solution was concentrated under reduced pressure, added with 100 mL of ethyl acetate, 100 mL of water and 50 mL of 1 M hydrochloric acid, extracted with ethyl acetate (100 mL.x.3). The combined organic phase was washed with saturated sodium chloride solution (50 mL.x.3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound tert-butyl(cis)-5-oxo-1, 3, 3a, 4, 6, 6a-hexahydrocyclopenta[e]pyrrole-2-carboxylate 5d (7.69 g, yield: 40.0percent).Step 3 tert-butyl (cis)-5-oxo-1, 3, 3a, 4, 6, 6a- hexahydrocyclopenta[c]pyrrole-2-carboxylate; tert-butyl N-allyl-N-prop-2-yne-carbamate 5c (16.70 g, 0.86 mol) was dissolved in 100 mL of dichloromethane followed by the addition of dicobalt octacarbonyl (29.40 g, 0.86 mol) and 31 mL of water. The resulting solution was heated to reflux and stirred for 3 hours, added with 10 mL of water. The reaction solution was concentrated under reduced pressure, added with 100 mL of ethyl acetate, 100 mL of water and 50 mL of 1 M hydrochloric acid, extracted with ethyl acetate (100 mL.x.3). The combined organic phase was washed with saturated sodium chloride solution (50 mL.x.3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound tert-butyl (cis)-5-oxo-1, 3, 3a, 4, 6, 6a-hexahydrocyclopenta[c]pyrrole-2-carboxylate 5d (7.69 g, yield: 40.0percent).