sodium methylate in N,N-dimethyl-formamide T=5 - 28°C; Inert atmosphere;

potassium phosphate; keto-reductase enzyme KRED-P1-B12; NADP; magnesium sulfate in water; dimethyl sulfoxide; isopropyl alcohol T=25 - 30°C; Enzymatic reaction;

2: 55.8 g / sodium methoxide / dimethylformamide View Scheme

1: With potassium carbonate in N,N-dimethyl-formamide T=20 - 25°C; 3 h; Large scale; 2: With dimethyl sulfate in N,N-dimethyl-formamide T=20 - 25°C; 3 h; Large scale;

hydrogenchloride T=25 - 35°C; 48 h;

1.1: sodium hydroxide; water / 2 h / 95 - 100 °C 1.2: 40 - 45 °C / pH 1.3 2.1: sodium methylate; (S)-2-carbomethoxypyrrolidine hydrochloride / tert-butyl methyl ether; methanol / 1.25 h / 25 - 60 °C / Reflux 3.1: toluene-4-sulfonic acid / 48 h / 25 - 35 °C View Scheme

1: 2-hydroxy methyl 3-methoxy-3,3-diphenylpropionate With [Cu(S,S)-t-Bu-box]OTf2 in dichloromethane T=0°C; 0.166667 h; Inert atmosphere; 2: 1-isocyanatopropane in dichloromethane T=0°C; 3 h; Inert atmosphere; optical yield given as percent eeenantioselective reaction;

1.1: sodium methylate / tetrahydrofuran / 2 h / -10 - -4 °C 1.2: 2.75 h / 0 - 35 °C 2.1: sodium hydroxide; water / 2 h / 95 - 100 °C 2.2: 40 - 45 °C / pH 1.3 3.1: sodium methylate; (S)-2-carbomethoxypyrrolidine hydrochloride / tert-butyl methyl ether; methanol / 1.25 h / 25 - 60 °C / Reflux 4.1: toluene-4-sulfonic acid / 48 h / 25 - 35 °C View Scheme

1.1: potassium carbonate / acetone / 0.67 h / 25 - 35 °C 1.2: 10 h / 55 - 60 °C 2.1: sodium hydroxide / water; methanol / 3 h / 25 - 60 °C 2.2: pH 5.8 View Scheme

potassium carbonate in N,N-dimethyl-formamide T=90 - 92°C; 1 h; Inert atmosphere;