Synthesis and resolution of nicotine
View Patent ↗The present disclosure generally relates to methods of preparing nicotine and resolving R,S nicotine to enrich the (S)(−) enantiomer. The method may comprise combining N-methyl-2-pyrrolidone or a salt thereof with a nicotinate compound in the presence of a solvent and a strong base to form 1-methyl-3-nicotinoyl-2-pyrrolidone or a salt thereof; and reducing the 1-methyl-3-nicotinoyl-2-pyrrolidone or salt thereof in solution with Na 2 S 2 O 4 to produce racemic nicotine or salt thereof. Resolving the racemic nicotine (or other enantiomeric mixture) may comprise combining the nicotine with (−)-O,O′-di-p-toluoyl-L-tartaric acid (L-PTTA).
1. A method of preparing a nicotine composition, the method comprising:
separating a salt from a solution comprising (−)—O,O′-di-p-toluoyl-L-tartaric acid (L-PTTA), (S)—(−)-nicotine, and (R)—(−)-nicotine, wherein the salt comprises (S)—(−)-nicotine and L-PTTA; and
separating (S)—(−)-nicotine from the salt;
wherein the nicotine composition has an enantiomeric excess of (S)—(−)-nicotine ranging from about 40% to 100%.
2. The method of claim 1 , wherein the enantiomeric excess of (S)—(−)-nicotine in the nicotine composition is greater than 90%.
3. The method of claim 1 , wherein a molar ratio of L-PTTA to a combination of (S)—(−)-nicotine and (R)—(−)-nicotine in the solution ranges from about 0.3 to about 1.3.
4. The method of claim 3 , wherein the molar ratio ranges from about 0.7 to about 0.8.
5. The method of claim 1 , wherein the solution comprises racemic nicotine.
6. The method of claim 5 , wherein the racemic nicotine is synthesized by reducing 1-methyl-3-nicotinoyl-2-pyrrolidone or a salt thereof with Na 2 S 2 O 4 .
7. The method of claim 1 , further comprising recrystallizing the salt after separating the salt from the solution.
8. The method of claim 1 , further comprising adding pure (S)—(−)-nicotine L-PTTA salt to the solution before separating the salt from the solution.
9. The method of claim 1 , further comprising recovering unresolved nicotine or L-PTTA from the solution after separating the salt from the solution.