Hydrochloric Acid → (3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride

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Reaction Steps

To a stirring solution of (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate (E-1, the first eluting enantiomer from step F, 44 mg, 0.134 mmol) in 1,4-dioxane (3 mL) at 0° C. was added 2 mL (8 mmol) of 4 M HCl in dioxane, and the resulting mixture was stirred at rt for 12 h. The solvent was removed under reduced pressure to afford (3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride (30 mg) as a white solid which was used without further purification. LCMS (Method J) RT=0.60 min, m/z 228.2 (M+H+). 1H NMR (400 MHz, methanol-d4) δ ppm 7.01-7.19 (m, 3H) 4.88-4.99 (m, 1H) 4.71-4.83 (m, 1H) 3.89 (s, 3H) 3.67-3.78 (m, 1H) 3.40-3.53 (m, 1H) 3.00-3.25 (m, 3H) 2.12-2.27 (m, 1H) 1.93-2.08 (m, 1H).

Provenance & Evidence