Benzyl Bromide → Methyl 2-Benzyl-3-[4-(4-Chlorophenyl)-4-fluoropiperidin-1-yl]propionate Hydrochloride

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Reaction Steps

A solution of methyl 3-[4-(4-chlorophenyl)-4-fluoropiperidin-1-yl]propionate (75 mg, 0.23 mmol) in toluene (5 mL) was placed under a dry nitrogen atmosphere and cooled in a dry ice acetone bath. A 1M solution of lithium hexamethyldisilazide (0.28 mL, 0.28 mmol) was then added drop-wise over 10 minutes. The resulting bright yellow solution was stirred for 1 hour then benzyl bromide (43 mg, 0.25 mmol) added in one portion. The reaction was then allowed to warm to room temperature with stirring over a 16 hour period then quenched by the addition of 25% aqueous ammonium chloride solution (10 mL). The resulting mixture was extracted with ethyl acetate (2×10 mL) and the combined extracts dried over magnesium sulfate, filtered and stripped to a viscous yellow oil. This oil was treated with 10% methanolic hydrogen chloride (5 mL) and the solution re-concentrated. The resulting oil was triturated with 1:1 ethyl acetate/heptanes (10 mL) to afford a light yellow solid which was collected by filtration. After drying under vacuum for 12 hours methyl 2-benzyl-3-[4-(4-chlorophenyl)-4-fluoropiperidin-1-yl]propionate hydrochloride was obtained as a light yellow solid in 44% yield.

Provenance & Evidence