N-ethyl-N,N-diisopropylamine in acetonitrile T=0°C; Addition; 1 h;

1: H2, Et3N / Raney nickel / methanol / 8 h / 2647.8 Torr 2: Et3N / CH2Cl2 / 4 h / Ambient temperature 3: 95 percent / trifluoroacetic anhydride, DMSO / CH2Cl2 / 1.5 h / -78 - -65 °C 4: 1.) lithium diisopropylamide / 1.) THF, below -65 deg C, 20 min, 2.a) THF, below -65 deg C, 1.5 h, b) to -10 deg C 5: 75 percent / potassium hydride / dimethylformamide / 1 h / 0 °C 6: 53 percent / O2 / PdCl2, CuCl / dimethylformamide; H2O / 19 h / 70 °C / other oxidants (without catalyst), solvents temperatures, reaction times 7: 1.) 0.6N aq. HCl, 2.) Jones reagent / 1.) THF, reflux, 3 h, 2.) acetone, 0 deg C, 40 min 8: H2 / 5percent Pd/C / methanol / 1 h 9: concd. HCl / 0.67 h / Heating 10: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 11: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 12: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 13: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 14: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 15: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: Et3N / CH2Cl2 / 4 h / Ambient temperature 2: 95 percent / trifluoroacetic anhydride, DMSO / CH2Cl2 / 1.5 h / -78 - -65 °C 3: 1.) lithium diisopropylamide / 1.) THF, below -65 deg C, 20 min, 2.a) THF, below -65 deg C, 1.5 h, b) to -10 deg C 4: 75 percent / potassium hydride / dimethylformamide / 1 h / 0 °C 5: 53 percent / O2 / PdCl2, CuCl / dimethylformamide; H2O / 19 h / 70 °C / other oxidants (without catalyst), solvents temperatures, reaction times 6: 1.) 0.6N aq. HCl, 2.) Jones reagent / 1.) THF, reflux, 3 h, 2.) acetone, 0 deg C, 40 min 7: H2 / 5percent Pd/C / methanol / 1 h 8: concd. HCl / 0.67 h / Heating 9: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 10: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 11: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 12: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 13: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 14: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 2: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 3: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 4: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 5: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 2: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 3: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 4: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 5: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 6: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 2: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 3: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 4: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: concd. HCl / 0.67 h / Heating 2: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 3: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 4: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 5: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 6: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 7: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: 95 percent / trifluoroacetic anhydride, DMSO / CH2Cl2 / 1.5 h / -78 - -65 °C 2: 1.) lithium diisopropylamide / 1.) THF, below -65 deg C, 20 min, 2.a) THF, below -65 deg C, 1.5 h, b) to -10 deg C 3: 75 percent / potassium hydride / dimethylformamide / 1 h / 0 °C 4: 53 percent / O2 / PdCl2, CuCl / dimethylformamide; H2O / 19 h / 70 °C / other oxidants (without catalyst), solvents temperatures, reaction times 5: 1.) 0.6N aq. HCl, 2.) Jones reagent / 1.) THF, reflux, 3 h, 2.) acetone, 0 deg C, 40 min 6: H2 / 5percent Pd/C / methanol / 1 h 7: concd. HCl / 0.67 h / Heating 8: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 9: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 10: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 11: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 12: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 13: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: 1.) lithium diisopropylamide / 1.) THF, below -65 deg C, 20 min, 2.a) THF, below -65 deg C, 1.5 h, b) to -10 deg C 2: 75 percent / potassium hydride / dimethylformamide / 1 h / 0 °C 3: 53 percent / O2 / PdCl2, CuCl / dimethylformamide; H2O / 19 h / 70 °C / other oxidants (without catalyst), solvents temperatures, reaction times 4: 1.) 0.6N aq. HCl, 2.) Jones reagent / 1.) THF, reflux, 3 h, 2.) acetone, 0 deg C, 40 min 5: H2 / 5percent Pd/C / methanol / 1 h 6: concd. HCl / 0.67 h / Heating 7: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 8: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 9: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 10: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 11: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 12: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme

1: H2 / 5percent Pd/C / methanol / 1 h 2: concd. HCl / 0.67 h / Heating 3: 2.) N,N'-dicyclohexylcarbodiimide, TEA / 1.) 70 deg C, 7 h, 2.) 55 deg C, 5.5 h 4: H2 / 5percent Pd/C / methanol / 1 h / Ambient temperature 5: 1.) N,N'-carbonyldiimidazole / 1.) DMF, acetonitrile, r.t., 1.5 h, 2.) r.t., overnight 6: 74 percent / p-carboxybenzenesulfonyl azide, TEA / ethyl acetate / 0.5 h / Ambient temperature 7: 74 percent / Rh2(OAc)4 / benzene / 0.05 h / Heating 8: N,N-diisopropylethylamine / acetonitrile / 1.5 h / -20 °C View Scheme