Phosphorus oxychloride → 2-Chloro-5-fluoro-1,3-benzoxazole

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Reaction Steps

The 2-mercapto-5-fluorobenzoxazole (2.0 g, 11.8 mmol) is slurried into POCl3 (9.7 mL, 104 mmol). The slurry is treated with PCl5 (3.0 g, 14.2 mmol) and 5.0 mL of anhydrous CH2Cl2. The mixture is stirred at room temperature for 5.5 hours. After this time excess POCl3 is removed under reduced pressure. The residue is treated with saturated aqueous NaHCO3 and the mixture is poured into a separatory funnel. The mixture is extracted with EtOAc and the combined extracts are washed with brine and dried over anhydrous Na2SO4. Filtration and concentration gives 1.76 g of 2-chloro-5-fluorobenzoxazole as a waxy solid. The crude chloride is used in the piperazine displacement reaction.

Provenance & Evidence