Example 1; Synthesis of (R)-2-amino-3-(1H-imidazol-4-yl)propanoic acid methyl ester dihydrochloride was carried out by improving the method reported by Cook et al. In a 200 L Schott glass reactor equipped with an air-driven stirrer, a high-efficiency condenser and a gas introduction port, 12.5 kg of L-histidine hydrochloride monohydrate was suspended in 130 L of methanol. Dry HCl gas was passed into the suspension while the mixture was heated to 55-65 °C until complete dissolution. The passage of HCl gas was continued until saturation, at which point it was stopped. Shortly after the solution was formed, a precipitation of the product began to appear. The mixture is stirred continuously and supplemented with additional passes of HCl gas every 1 hour and 15 minutes; the mixture is heated under mild reflux conditions for 8 hours. After the reaction is complete, it can be kept warm for 6-8 hours. Subsequently, 40 L of ethyl acetate is added, stirred for 1 hour and filtered. The filter cake was washed with 10 L of isopropyl ether and the resulting white crystalline product was air dried. The yield was 95%. The melting point was 102-103 °C (literature value 102-103 °C). Spinodal [α]25D = +3.5° (c=2, H2O).1H NMR (D2O) data: δ 3.4 (t, 2H), 3.9 (s, 3H), 4.5 (s, 2H), 7.4 (s, 1H), 8.5 (s, 1H).
