Regioselective halogenation of nicotine and substituted nicotines
A first aspect of the present invention is a method for of making a compound of Formula Ia or Formula Ib: wherein X is halo, by (a) metalating a precursor compound to form an organometallic intermediate, and then reacting the organometallic intermediate with a halogenating agent to produce the compound of Formula Ia or Formula Ib.
1. A compound of Formula III:
wherein:
R 4 and R 5 are H, alkyl or aryl, or R 4 is —SiR 20 R 21 R 22 , wherein R 20 , R 21 and R 22 are each independently alkyl or ary;
R 6 is H, alkyl, aryl, alkoxy or halo;
R 7 is H, alkyl or aryl; and
R 30 , R 31 and R 32 are each alkyl or aryl.
2. The compound of claim 1 , wherein R 4 and R 5 are H.
3. The compound of claim 1 , wherein R 6 is H.
4. The compound of claim 1 , wherein R 7 is methyl.
5. The compound of claim 1 , wherein R 30 , R 31 and R 32 are each cyclohexyl.
6. The compound of claim 1 , wherein:
R 4 , R 5 and R 6 are each H;
R 7 is methyl; and
R 30 , R 31 and R 32 are each cyclohexyl.