ethyl 2-diazo-3-oxo-3-phenylpropanoate

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7.66 g of ethyl α-diazobenzoylacetate, 3.8 g of p-cresol and 150 mg of rhodium(II) acetate in 40 cc of carbon tetrachloride was stirred at a temperature of 40-50° C. for 2 hours. After cooling, the insoluble materials were filtered off and the solvent was distilled off. The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2) to obtain 2.59 g of compound E. Yield: 24.7%. After cooling the insoluble materials were filtered off the solvent was distilled off The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2)

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7.66 g of ethyl α-diazobenzoylacetate, 3.8 g of p-cresol and 150 mg of rhodium(II) acetate in 40 cc of carbon tetrachloride was stirred at a temperature of 40-50° C. for 2 hours. After cooling, the insoluble materials were filtered off and the solvent was distilled off. The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2) to obtain 2.59 g of compound E. Yield: 24.7%. After cooling the insoluble materials were filtered off the solvent was distilled off The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2)

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7.66 g of ethyl α-diazobenzoylacetate, 3.8 g of p-cresol and 150 mg of rhodium(II) acetate in 40 cc of carbon tetrachloride was stirred at a temperature of 40-50° C. for 2 hours. After cooling, the insoluble materials were filtered off and the solvent was distilled off. The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2) to obtain 2.59 g of compound E. Yield: 24.7%. After cooling the insoluble materials were filtered off the solvent was distilled off The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2)

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

実験手順: A flask containing a mixture of ethyl 2-diazo-3-oxo-3-phenylpropanoate (16C) (2.80 g, 12.84 mmol), 16B (4.45 g, 16.05 mmol) from previous step, and 128 mL of 1:1 toluene:dichloroethane was heated at 80° C. for about 10 minutes. A suspension of rhodium octanoate dimer (0.20 g, 0.26 mmol) in 25 mL toluene was added dropwise to the reaction mixture via an addition funnel. The reaction was held at 80° C. for an additional hour after the addition was completed. After the disappearance of 16C, the reaction was cooled to RT. Approximately 8 mL of TFA was then added and the reaction was allowed to stir overnight at RT. The reaction mixture was concentrated to a green oil then purified by flash chromatography on silica gel using 5% methanol/DCM to afford benzyl 3-(4-(ethoxycarbonyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxylate (16D) as a tan solid (2.50 g, 42%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.94 (t, J=7.07 Hz, 3H) 1.07-1.18 (m, 2H) 1.24 (br. s., 1H) 1.62-1.78 (m, 2H) 2.36-2.43 (m, 1H) 2.59-2.68 (m, 1H) 3.46-3.58 (m, 2H) 3.96 (q, J=6.91 Hz, 2H) 4.99 (s, 1H) 7.26-7.51 (m, 11H) 10.97 (s, 1H) ESI-MS: m/z 450.1 (M+H)+. A flask containing was added dropwise to the reaction mixture via an addition funnel The reaction was held at 80° C. for an additional hour after the addition The reaction mixture was concentrated to a green oil then purified by flash chromatography on silica gel using 5% methanol/DCM

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

実験手順: A flask containing a mixture of 15B (3.20 g, 12.87 mmol), ethyl 2-diazo-3-oxo-3-phenylpropanoate (15C) (2.25 g, 10.31 mmol), and 103 mL of 1:1 toluene:dichloroethane was heated at 80° C. for about 10 minutes. A suspension of rhodium octanoate dimer (0.16 g, 0.21 mmol) in 25 mL toluene was added dropwise to the reaction mixture via addition funnel. The reaction was held at 80° C. for an additional hour after addition was completed. After the disappearance of 15C, the reaction was cooled to RT. Approximately 8 mL of TFA was then added and the reaction was allowed to stir overnight at RT. The reaction mixture was concentrated to a green oil then purified by flash chromatography on silica gel using 5-40% ethyl acetate/hexanes to afford the desired product ethyl 1-((1R,2R)-2-(benzyloxy)cyclohexyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylate as a tan solid (15D) (2.20 g, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96 (t, J=7.07 Hz, 4H) 1.16 (d, J=12.13 Hz, 1H) 1.56-1.67 (m, 2H) 1.72 (d, J=12.13 Hz, 1H) 2.11 (d, J=6.82 Hz, 1H) 2.32 (d, J=8.84 Hz, 1H) 3.25 (br. s., 1H) 3.98 (q, J=7.07 Hz, 2H) 4.19-4.31 (m, 3H) 4.51 (d, J=11.87 Hz, 1H) 7.15 (d, J=7.33 Hz, 2H) 7.23-7.34 (m, 1H) 7.28 (dd, J=7.71, 1.64 Hz, 4H) 7.43 (br. s., 3H) 10.86 (s, 1H). ESI-MS: m/z 421.4 (M+H)+. A flask containing was added dropwise to the reaction mixture via addition funnel The reaction was held at 80° C. for an additional hour after addition The reaction mixture was concentrated to a green oil then purified by flash chromatography on silica gel using 5-40% ethyl acetate/hexanes

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7.66 g of ethyl α-diazobenzoylacetate, 3.8 g of p-cresol and 150 mg of rhodium(II) acetate in 40 cc of carbon tetrachloride was stirred at a temperature of 40-50° C. for 2 hours. After cooling, the insoluble materials were filtered off and the solvent was distilled off. The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2) to obtain 2.59 g of compound E. Yield: 24.7%. After cooling the insoluble materials were filtered off the solvent was distilled off The crude product thus obtained was purified by a silica gel column chromatography (eluent: chloroform/hexane=1/2)