Processes and intermediates for making sweet taste enhancers
The present invention includes methods/processes and intermediates for preparing compounds having structural Formula (I): wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.
1. A compound having structural Formula (IIIc):
wherein
R 1 is —CN, or —C(O)N(R 2 ) 2 ;
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene;
R 8 is C 1 -C 12 alkyl; and
R 2 is C 1 -C 12 alkyl.
2. A process of preparing a compound having structural Formula (IIIa):
comprising reducing a compound having structural Formula (IV), or treating a compound having structural Formula (IV) with ammonia,
wherein
R 4 is nitro or halo; and
X is —Y—C(O)—NHR 2 ,
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 2 is hydrogen or C 1 -C 12 alkyl.
3. A compound having structural Formula (IV):
wherein
R 4 is nitro, —NH 2 , or halo; and
X is —Y—C(O)—NHR 2 ,
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 2 is hydrogen or C 1 -C 12 alkyl.
4. A process of preparing the compound of claim 3 , comprising reacting a compound having structural Formula (V)
with X—OH in the presence of NaH, NaHMDS, KO-t-Bu or K 2 CO 3 ;
wherein
R 4 is nitro, —NH 2 , or halo; and
R 5 is nitro or halo.
5. A process of preparing the compound of claim 3 , comprising reacting a compound having structural Formula (VI)
with X—R 6 in the presence of NaH, NaHMDS, KO-t-Bu or K 2 CO 3 or an activating reagent;
wherein
R 4 is nitro, —NH 2 , or halo; and
R 6 is a leaving group selected from halo, —OMs, —OTs, and —OTf.
6. A process of preparing a compound having structural Formula (IIIc):
comprising reacting a compound having structural Formula (X)
with R 8 —NH 2 , in the presence of an activating reagent;
wherein
R 1 is —CN or —C(O)NH 2 ;
Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and
R 8 is C 1 -C 12 alkyl; and
R 9 is hydrogen or C1-C12 alkyl.
7. A process of preparing a compound having structural Formula (IIIc1):
comprising reacting HO—Y—C(O)—NHR 8 with
in the presence of a base to form a first mixture solution,
concentrating the first mixture solution to form a concentrated first mixture solution,
wherein the volume of the concentrated first mixture solution is equivalent to or less than
about 50% of the volume of the first mixture solution,
diluting the concentrated first mixture solution with an ether to form a second mixture solution,
concentrating the second mixture solution to form a concentrated second mixture solution, wherein the volume of the concentrated second mixture solution is equivalent to or
less than about 50% of the volume of the second mixture solution,
diluting the concentrated second mixture solution with ethyl acetate to form a third mixture solution, and
concentrating the third mixture solution to form a concentrated third mixture solution,
wherein the compound having structural Formula (IIIc1) precipitates as a solid;
wherein
Y is C1-C12 alkylene or C1-C12 alkenylene; and
R 8 is C1-C12 alkyl.
8. The process of claim 5 , wherein X is alkyl or alkenyl.
9. The compound of claim 1 having the formula:
10. The process of claim 2 , wherein the compound of structural Formula (IIIa) has the formula:
comprising reducing a compound having the structural formula:
or treating a compound having the formula:
with ammonia.
11. The compound of claim 3 having the formula:
wherein R 4 is nitro, —NH 2 , or fluoro.