| 摘要 |
A process for preparing (R)-2-hydroxy-2-(chlorophenyl)acetic methyl ester sulfate is provided to simplify the preparation procedure, improve preparation yield and purity of compound, and enhance safety to human by removing use of toxic materials in the preparation. A process for preparing (R)-2-hydroxy-2-(chlorophenyl)acetic methyl ester sulfate represented by the formula(7) comprises : a step(a) of dissolving thiophene in organic solvent and reacting the solution in the presence of base and catalyst to prepare N-benzyl-(2-thiopene-2-yl-ethyl)amine represented by the formula(1); a step(b) of dissolving the compound represented by the formula(1) in solvent, adding strong acid into the solution, and heating and stirring the solution to prepare N-benzyl-4,5,6,7-tetrahydro-thieno-[3,2-c]pyridine represented by the formula(2); a step(c) of dissolving the compound represented by the formula(2), adding organic acid and palladium catalyst into the solution at room temperature to prepare 4,5,6,7-tetrahydro-thieno-[3,2-c]pyridine represented by the formula(3), and introducing HCl gas into the compound to prepare hydrochlorate of the compound represented by the formula(3); a step(d) of dissolving (R)-2-hydroxy-2-(2-chlorophenyl) acetate in organic solvent, adding a reaction catalyst into the solution, and stirring the solution to prepare the compound represented by the formula(4), and reacting the compound represented by the formula(4) with sulfonate reaction reagent in the presence of base to prepare (R)-2-benzenesulfonyloxy-2-(2-chlorophenyl)acetic methyl ester represented by the formula(5); a step(e) of dissolving the hydrochlorate of the compound represented by the formula(3) in organic solvent, adding base, reacting the solution with the compound represented by the formula(5) dissolved in dichloromethane to prepare (S)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydro-thieno-[3,2-c]pyridine)acetic methyl ester represented by the formula(6); and a step(f) of dissolving the compound represented by the formula(6) in organic solvent and adding weak sulfuric acid into the solution to prepare (S)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydro-thioeno-[3,2-c]pyridine)acetic methyl ester sulfate represented by the formula(7), and freeze-drying the compound represented by the formula(7). Further, an reacting temperature is -40 to 0 °C, and the organic solvent is one or mixture of anhydrous tetrahydrofuran and dioxane in the step(a).
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