Sodium Hydroxide → 1-Chloro-6-fluoroisoquinoline

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Reaction Steps

To a solution of 6-fluoroisoquinoline N-oxide (3 g, 18 mmol) in CHCl3 (50 mL) is added phosphorus oxychloride (5 mL, 54 mmol). The reaction mixture is refluxed for 2 h. The reaction mixture is poured into ice, and the pH is brought to pH 8-9 with 5 M NaOH. The aqueous phase is extracted with CH2Cl2 (3×). The combined organic layers are dried over MgSO4, and evaporated. Purification of the crude product by Biotage column eluted with 0-30% EtOAc/hexanes afforded 1.06 g (35%) of 1-chloro-6-fluoro-isoquinoline. LC/MS m/z=182 [M+H]+.

Provenance & Evidence