US 9,809,567 B2
Synthesis and resolution of nicotine
Bert Willis, Mills River, NC (US); Mohammed Moinuddin Ahmed, Brevard, NC (US); Wesley Freund, Arden, NC (US); and Douglas Sawyer, Gilbert, AZ (US)
Assigned to NJOY, LLC, Scottsdale, AZ (US)
Filed by NJOY, Inc., Scottsdale, AZ (US)
Filed on Dec. 8, 2015, as Appl. No. 14/962,072.
Claims priority of provisional application 62/089,623, filed on Dec. 9, 2014.
Prior Publication US 2016/0326134 A1, Nov. 10, 2016
Int. Cl. C07D 401/04 (2006.01)
CPC C07D 401/04 (2013.01) 17 Claims
 
1. A method of preparing (S)-(−)-nicotine or a salt thereof, the method comprising:
combining N-methyl-2-pyrrolidone or a salt thereof with a nicotinate compound in the presence of a solvent and a base to form 1-methyl-3-nicotinoyl-2-pyrrolidone or a salt thereof;
reducing the 1-methyl-3-nicotinoyl-2-pyrrolidone or salt thereof in solution with Na2S2O4 to produce racemic nicotine or a salt thereof;
enriching (S)-(−)-nicotine by combining the racemic nicotine with (−)-O,O′-di-p-toluoyl-L-tartaric acid (L-PTTA) to produce a nicotine-L-PTTA salt; and
isolating the (S)-(−)-nicotine from the nicotine-L-PTTA salt.