无水氟化试剂可以通过SNAr氟化交换掉芳环的卤素，这在很多文献上已经有报道。
OPRD在2021年4月份的最新报道中提到，通过小试筛选，他们发现无水的四甲基氟化铵(TMAF, anh)可以通过氟氯交换成功实现噻唑环的氟化。
但是市场上可商业获得的TMAF都是四水合物（TMAF-4H2O），很难买到无水的TMAF，而且作者期望他们的工艺是能用于放大生产的，因此能够稳定可靠的获得这种无水TMAF试剂就显得非常重要。但是，TMAF-4H2O中的水分子是以氢键的方式与氟结合的。普通的处理方法很难除去其中的水份，只有用醇类才能破坏原有的氢键，将原来的水合物结构替换为溶剂络合物结构。
于是，他们对不同含水量或经不同处理方式处理过的TMAF水合物进行了测试。
实验结果显示，采用异丙醇共沸除水，再用DMF溶剂置换异丙醇的处理方式，可以把TMAF含水量降低到0.16%，满足反应需要。
具体实施办法如下：
TMAF·4H2O (32.5 g, 200 mmol, 10.5 equiv) was charged into a three-neck round-bottom flask followed by IPA (200 mL, 6.1 mL/g relative to TMAF·4H2O). The reaction mixture was concentrated and azeotropically distilled with IPA 10 times until the water content was measured to be <0.2% (by KF analysis). DMF (200 mL, 6.1 mL/g) was next added to the reaction mixture. The mixture was concentrated with DMF added back 10 times until the IPA concentration was measured to be <60 ppm. The TMAF/ DMF solution was adjusted to provide a final concentration of 20 mL/g DMF relative to compound 2a (100 mL). Compound 2a (5.0 g, 19.0 mmol) was charged into the flask. The reaction mixture was heated to 100 °C for 2 h and then cooled to 25 °C. 2-MeTHF (100 mL, 20 mL/g) was added, followed by addition of saturated NH4Cl (150 mL, 30 mL/g). The mixture was stirred for 17 h, and then, the layers were separated. The organic layer was concentrated to dryness, and the residue was purified via flash column chromatography (2:1 petroleum ether/EtOAc). Fractions containing the desired product were combined and concentrated to provide fluorothiazole 1a (1.4 g) as a yellow solid in 30% isolated yield (96.2% purity). 1 H NMR (400 MHz, CDCl3, ppm): δ 9.933 (1H, s, CHO), 1.567 (9H, s, CCH3); 13C NMR (400 MHz, CDCl3, ppm): δ 179.2, 164.9, 164.7, 164.1, 161.4, 151.7, 107.2, 107.1, 84.7. ESI-MS m/z: C9H11FN2O3S [M + 1]+ , 247.05.
从下图可以看出，除水效果非常显著，经五次异丙醇共沸以后，含水量可以从8.5%降低到0.2%：
Org.Process Res. Dev; https://doi.org/10.1021/acs.oprd.1c00042
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