1: With potassium tert-butylate 2: With sodium hydroxide 3: With hydrogenchloride Further stages.;

sodium hydroxide in ethanol T=0°C; 3 h;

1: NaOH / aq. ethanol / 5 h / 0 °C 2: toluene / 3 h / Heating 3: NaOH / aq. ethanol / 3 h / 0 °C View Scheme

2,2'-azo-bisisobutyronitrile in 1,4-dioxane T=100°C; 48 h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(i) (decarboxylation), (ii) aq. NaOH, EtOH; Multistep reaction;

sodium hydroxide

T=125°C;

1.1: alcaligenes sp. D-aminoacylase; tris(hydroxymethyl)methylamine hydrochloride / 24 h / 40 °C / pH 8 / |Resolution of racemate; |Large scale; |Enzymatic reaction 1.2: 5 - 10 °C / pH 7.5 - 8.5 / |Large scale 2.1: thionyl chloride / 0 - 20 °C 3.1: formic acid / 72 h / 25 °C 4.1: tert-butyl methyl ether; chirazyme L9 (Mucormiehei, Roche) / aq. phosphate buffer / 96 h / 20 °C / pH 7 / |Resolution of racemate; |Enzymatic reaction 5.1: palladium 10 on activated carbon; hydrogen / ethyl acetate / 1500.15 Torr / |Inert atmosphere View Scheme

1: 2-acetylamino-4-pentenoic acid With thermococcus litoralis L-aminoacylase; tris(hydroxymethyl)methylamine hydrochloride T=70°C; pH=8; Resolution of racemateLarge scaleEnzymatic reaction; 2: benzyl chloroformate With sodium hydroxide in tetrahydrofuran; water T=5 - 10°C; pH=7.5 - 8.5; Large scale;

1: 95 percent / aq. LiOH / 12 h / 38 °C / porcine kidney acylase I 2: aq. K2CO3 View Scheme