We discovered that copper present in laboratory tap water could catalyze an addition reaction of the hydroxyl group of acetylnaltrexone to isocyanate. The first pilot manufacturing of naldemedine tosylate encountered an unexpected problem in which the addition reaction was seriously delayed. Detailed investigations showed that the low copper content in pilot tap water led to a reduced reaction rate. This discovery allowed us to establish a robust manufacturing process by adding a copper catalyst. Since unintended contamination by metal catalysts can confuse chemists, we share our experience with the hope that our findings will raise awareness of contamination issues among researchers.

中文翻译：

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自来水中存在的铜催化醇与异氰酸酯的加成反应：甲苯磺酸纳拉美定的稳健制造工艺

我们发现实验室自来水中存在的铜可以催化乙酰纳曲酮的羟基与异氰酸酯的加成反应。首次中试生产甲苯磺酸萘美定遇到了一个意想不到的问题，即加成反应严重延迟。详细调查表明，中试自来水中的低铜含量导致反应速率降低。这一发现使我们能够通过添加铜催化剂来建立强大的制造工艺。由于金属催化剂的意外污染会使化学家感到困惑，因此我们分享我们的经验，希望我们的发现能够提高研究人员对污染问题的认识。