5-Methyltetrahydrofolate (5-MTHF) is an active form of folic acid (FA) and an essential micronutrient preventing anemia and numerous other adverse health conditions such as cardiovascular disease and cancer. Herein, a continuous flow sequence synthesis of 5-MTHF from FA was developed, involving three elementary steps: catalytic hydrogenation of FA to tetrahydrofolic acid (THFA), methylenation of THFA with formaldehyde, and hydrogenation of the methylenation intermediates to 5-MTHF. This process features an expeditious synthesis of 5-MTHF in an integrated flow platform with water as the sole solvent and without any intermediate purification. The overall yield of this three-step flow process was up to 53.54% in a total residence time of 71.4 min. The separated yield of 5-MTHF reached 49.3%.

中文翻译：

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由叶酸连续流合成 5-甲基四氢叶酸

5-甲基四氢叶酸 (5-MTHF) 是叶酸 (FA) 的活性形式，也是预防贫血和心血管疾病和癌症等许多其他不良健康状况的必需微量营养素。在此，开发了从 FA 连续流动顺序合成 5-MTHF 的方法，涉及三个基本步骤：FA 催化氢化为四氢叶酸（THFA）、THFA 用甲醛亚甲基化以及亚甲基化中间体氢化为 5-MTHF。该工艺的特点是在集成流动平台中以水为唯一溶剂快速合成 5-MTHF，无需任何中间纯化。该三步流程在总停留时间71.4分钟内的总收率高达53.54%。 5-MTHF的分离收率达到49.3%。