Pyridine → Topiramate

Participants

Reaction Steps

Under nitrogen, a solution of the alcohol of Example 1 (15.0 g, 0.0576 mol) and pyridine (15 mL, 0.18 mol) in methylene chloride (60 mL) was cooled to -40° C. in a dry ice/isopropanol bath. With stirring, a solution of sulfuryl chloride (16.0 g, 0.118 mol) in methylene chloride (10 mL) was added gradually (approx. 50 minutes) so that the temperature did not exceed -25° C. The ice bath was removed as soon as the addition was complete and the reaction mixture stirred for an additional 2 h. During this time the light yellow precipitate became a clumpy brown solid. Solvent was removed in vacuo to yield a sticky, brown residue. The residue was dissolved in 100 mL methylene chloride and anhydrous ammonia was bubbled through the mixture overnight at ambient temperature. The dark reaction mixture was concentrated in vacuo to give 47.7 g of the title compound as a black residue. The crude product was found to be 15.10% pure by GLC giving a corrected yield of 36.83 %.

Provenance & Evidence