Pinacol → 5-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridine

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Reaction Steps

A flask fitted with a Dean-Stark trap was charged with a solution of 5-chloro-2-fluoronicotinaldehyde, 27, (8.95 g, 56.10 mmol) and 2,3-dimethylbutane-2,3-diol (8.00 g, 67.70 mmol) and p-toluene sulfonic acid mono hydrate (0.54 g, 2.81 mmol) in toluene (250 mL) and heated to vigorous reflux for 3 hr. The mixture was cooled, diluted with EtOAc, washed with NaHCO3 (2×) and brine (1×). The organic phase was dried over Na2SO4, filtered through a silica plug and concentrated in vacuo. A crystalline solid formed on standing (14.47 g): 1H NMR (300.0 MHz, CDCl3) δ 8.12 (s, 1H), 7.97 (dd, J=2.7, 7.8 Hz, 1H), 6.08 (s, 1H), 1.33 (s, 3H) and 1.26 (s, 3H) ppm.

Provenance & Evidence