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Stage #1: D-o-methylserine With bis(trichloromethyl) carbonate In tetrahydrofuran Reflux;
Stage #2: benzylamine In ethyl acetate at 20℃; for 2h;
Stage #3: acetic anhydride In dichloromethane at 20℃; for 2h;
10.3
O-Methyl-D-serine (1.19 g, 0.01 mol) was suspended in tetrahydrofuran (40 mL). The suspension was heated to reflux and treated dropwise with a solution of triphosgene (1.09 g) and tetrahydrofuran (30 mL). The residual cloudiness dispersed into solution. The reaction mixture was stirred overnight at room temperature, then filtered to clarity. The solvent was completely removed by rotary evaporation to afford an oil (1.06 g, 73.7%)). This material was dissolved in ethyl acetate (20 mL) and treated withbenzylamine (0.78 g) at room temperature. The reaction mixture was stirred for 2 hours and then washed with water (2 x 3 mL). The solvent was completely removed from the organic phase by rotary evaporation to afford an oil (1.12 g). The resulting crude material was dissolved in dichloromethane (25 mL). After the addition of acetic anhydride (0.82 g, 0.08 mol), the reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was successively extracted with water (5 mL), 1M hydrochloric acid (5 mL), 5% aqueous sodium hydrogencarbonate solution (5 mL) and water (5 mL). The solvent was completely removed from the organic phase by rotary evaporation to afford the title compound (1.20 g, 88.9%>) as a colourless crystalline solid. HPLC: 93.46%) (R) isomer.
Into a 250 mL round-bottomed flask equipped with a stirrer, reflux condenser and thermometer was added O-methyl-D,L-serine (5 g) in 90: 10 methanol/water (25 mL). N- Acetyl-D-phenylalanine (8.70 g) was added in one portion and the mixture heated to 50C overnight. The suspension was cooled to room temperature and filtered, and the solid was rinsed with 90: 10 methanol/water (5 mL) and dried at 40C under vacuum for 3 h. The N- acetyl-D-phenylalanine salt of 0-methyl-D-serine (3.4 g, 25%) was obtained as a white solid with a chiral purity >90%. Regeneration of the title compound could be effected by adjustment of the pH to 1-2 by treatment with HCl, followed by extraction into an organic solvent and subsequent adjustment of the pH to ~7 with NaOH.
210 g
2) The reaction flask was charged with 1500 g of acetic acid followed by addition of 260 g of <strong>[19794-53-7]O-methyl-DL-serine</strong>, D-tartaric acid 315 g, and salicylaldehyde 7.5 g. Heating to 63C for 11 hours. Cooled to 20C crystallization 2 hours. Filtered to obtain O-methyl-D-serine complex salt 527 g. 3) A reaction flask was charged with 1400 g of a 70% (v / v) aqueous methanol solution. 527 g of O-methyl-D-serine double salt was added. Adjust the pH to 7-8 with ammonia water. The crystals were crystallized for 2 hours. 210 g of O-methyl-D-serine was obtained by filtration. The detection, content: greater than 98.5%, chiral purity: greater than 99.9%.