This article describes the use of tetramethylammonium fluoride tetrahydrate (TMAF·4H₂O) for the large-scale preparation of a challenging 4-fluorothiazole. Commercially available TMAF·4H₂O was procured on a large scale and rigorously dried by distillation with isopropyl alcohol and then dimethylformamide at elevated temperature. This method of drying provided anhydrous TMAF [TMAF (anh)] containing <0.2 wt % water and <60 ppm isopropanol. The use of TMAF (anh) was essential for production of the 4-fluorothiazole. When the chlorothiazole starting material was treated with other anhydrous fluoride sources, poor conversion of the starting material or potential safety issues were observed. S_NAr fluorination using dried TMAF·4H₂O was carried out at a 45.1 kg scale at 95–100 °C to produce 36.8 kg of 4-fluorothiazole 1b.

中文翻译：

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四甲基氟化铵四水合氟化物，用于4-氯噻_唑的S _N Ar氟化生产规模

本文介绍了使用四水合四甲基氟化铵（TMAF·4H ₂ O）大规模制备具有挑战性的4-氟噻唑。大规模采购可商购的TMAF·4H ₂ O，并先在异丙醇中蒸馏，然后在高温下用二甲基甲酰胺蒸馏，将其严格干燥。该干燥方法提供了包含＜0.2重量％的水和＜60ppm的异丙醇的无水TMAF [TMAF（anh）]。TMAF（anh）的使用对于生产4-氟噻唑至关重要。当氯噻唑起始原料用其他无水氟化物源处理时，观察到起始原料转化率低或潜在的安全问题。使用干燥的TMAF·4H ₂进行S _N Ar氟化O在95–100°C下以45.1 kg的比例进行氧化，生成36.8 kg的4-氟噻唑1b。