Processes and intermediates for making sweet taste enhancers

1. A compound having structural Formula (II)

wherein

R 1 is —CN, —C(O)OR 2 , or —C(O)NH 2 ;

X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl; and

R 2 is hydrogen or C 1 -C 12 alkyl.

2. A process of preparing a compound having structural Formula (IIIa):

comprising

i) reducing a compound having structural Formula (IV) where R 4 is nitro to provide the compound having structural Formula (IIIa), or

ii) treating a compound having structural Formula (IV) where R 4 is halo with ammonia to provide the compound having structural Formula (IIIa),

wherein

R 4 is nitro or halo; and

X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

3. The process of claim 2 , comprising reducing the compound having structural Formula (IV) to provide the compound of Formula (IIIa), where R 4 is nitro.

4. The process of claim 2 , comprising treating the compound having structural Formula (IV) with ammonia to provide the compound of Formula (IIIa), where R 4 is halo.

5. A process of preparing a compound having structural Formula (IIc):

comprising reacting a compound having structural Formula (IX)

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;

R 8 is C 1 -C 12 alkyl; and

R 9 is hydrogen or C 1 -C 12 alkyl.

6. A process of preparing a compound having structural Formula (IIc1):

comprising:

adding a solution of a compound having structural Formula (IIIc1)

in a mixed solvent of methylene chloride and dimethylacetamide to a solution of Cl—S(O) 2 —NH 2 in methylene chloride and optionally an additional solvent to form a mixture;

maintaining the mixture at about room temperature for about 6 to about 18 hours; and

extracting the mixture with an aqueous solution of a hydroxide or alkoxide base to form an extracted basic solution wherein the compound having structural formula (IIc1) is stabilized,

wherein:

Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and

R 8 is C 1 -C 12 alkyl.

7. The process of claim 6 , wherein the solution is Cl—S(O) 2 —NH 2 in methylene chloride and acetonitrile.

8. A process of preparing a compound having structural Formula (IIc1):

comprising:

adding a solution of a compound having structural Formula (IIIc1)

in a mixed solvent of methylene chloride and dimethylacetamide to a solution of Cl—S(O) 2 —NH 2 in methylene chloride and optionally an additional solvent to form a first mixture;

maintaining the first mixture at about room temperature for about 6 to about 18 hours;

mixing an aqueous solution of NaHCO 3 with the first mixture to form a second mixture, wherein the second mixture is maintained at a temperature of about 45° C. or below during the addition of the aqueous solution of NaHCO 3 ; and

extracting the second mixture with an aqueous solution of a hydroxide or alkoxide base to form an extracted basic solution wherein the compound having structural formula (IIc1) is stabilized,

wherein:

Y is C 1 -C 12 alkylene or C 1 -C 12 alkenylene; and

R 8 is C 1 -C 12 alkyl.

9. 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 and optionally washing the second mixture solution with water or an aqueous 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 and optionally diluting the concentrated third mixture solution with an alkane hydrocarbon solvent;

wherein

Y is C 1 -C 12 alkylene; and

R 8 is C 1 -C 12 alkyl.

10. The process of claim 9 comprising diluting the concentrated third mixture solution with an alkane hydrocarbon solvent.

11. The process of claim 9 comprising washing the second mixture solution with water or an aqueous solution.