1: ethyl (2R,3R,4S)-(+)-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylate, (S)-(+)-mandelate With sodium hydrogencarbonate in water; ethyl acetate T=25°C; 2: BrCH2CONBu2 With N-ethyl-N,N-diisopropylamine in acetonitrile T=10°C; 12 h; 3: With hydrogenchloride; sodium hydroxide more than 3 stages;

1: ethyl (2R,3R,4S)-(+)-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylate, (S)-(+) mandelate With sodium hydrogencarbonate in water; ethyl acetate T=25°C; 2: BrCH2CONBu2; N-ethyl-N,N-diisopropylamine in ethyl acetate; acetonitrile T=110°C; 16 h;

1: With sodium hydroxide; ethanol; water T=60°C; 4 h; 2: With hydrogenchloride in ethanol; water; ethyl acetate pH=5; Product distribution / selectivity;

N-ethyl-N,N-diisopropylamine in acetonitrile

1: 78 percent / DBU / tetrahydrofuran; propan-2-ol / 4 h / Ambient temperature 2: 12.34 g / H2 / Raney nickel / ethanol / 3040 Torr 3: 1.) sodium cyanoborohydride, 2.) bromocresol green, conc. HCl / 1.) THF, EtOH, 2.) THF, EtOH, 20 min 4: 2.775 g / C2H5ONa / ethanol / Heating 5: 91 percent / CH2Cl2 / 1 h / Ambient temperature 6: 95 percent / NaOH 7: 1.) Et3N, t-BuCOCl, 2.) n-BuLi 8: 4 N aq. HCl / dioxane 9: iPr2NEt / acetonitrile 10: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme

1: 12.34 g / H2 / Raney nickel / ethanol / 3040 Torr 2: 1.) sodium cyanoborohydride, 2.) bromocresol green, conc. HCl / 1.) THF, EtOH, 2.) THF, EtOH, 20 min 3: 2.775 g / C2H5ONa / ethanol / Heating 4: 91 percent / CH2Cl2 / 1 h / Ambient temperature 5: 95 percent / NaOH 6: 1.) Et3N, t-BuCOCl, 2.) n-BuLi 7: 4 N aq. HCl / dioxane 8: iPr2NEt / acetonitrile 9: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme

1: 78 percent / DBU / tetrahydrofuran; propan-2-ol / 4 h / Ambient temperature 2: 12.34 g / H2 / Raney nickel / ethanol / 3040 Torr 3: 1.) sodium cyanoborohydride, 2.) bromocresol green, conc. HCl / 1.) THF, EtOH, 2.) THF, EtOH, 20 min 4: 2.775 g / C2H5ONa / ethanol / Heating 5: 91 percent / CH2Cl2 / 1 h / Ambient temperature 6: 95 percent / NaOH 7: 1.) Et3N, t-BuCOCl, 2.) n-BuLi 8: 4 N aq. HCl / dioxane 9: iPr2NEt / acetonitrile 10: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme

1: 1.) sodium cyanoborohydride, 2.) bromocresol green, conc. HCl / 1.) THF, EtOH, 2.) THF, EtOH, 20 min 2: 2.775 g / C2H5ONa / ethanol / Heating 3: 91 percent / CH2Cl2 / 1 h / Ambient temperature 4: 95 percent / NaOH 5: 1.) Et3N, t-BuCOCl, 2.) n-BuLi 6: 4 N aq. HCl / dioxane 7: iPr2NEt / acetonitrile 8: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme

1: iPr2NEt / acetonitrile 2: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme

1: 95 percent / 1,2-dichloro-ethane / 0.83 h / -20 - 20 °C 2: iPr2NEt / acetonitrile 3: 78 percent / aq. LiOH, 30percent aq. H2O2 / tetrahydrofuran / 0.5 h View Scheme