Processes and intermediates for making sweet taste enhancers

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

• comprising
• i) reducing a compound having structural Formula (IV) where R4 is nitro to provide the compound having structural Formula (IIIa), or
• ii) treating a compound having structural Formula (IV) where R4 is halo with ammonia to provide the compound having structural Formula (IIIa),
• wherein
• R4 is nitro or halo;
• and
• X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

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

• comprising reacting a compound having structural Formula (IX)
• with R8—NH2, in the presence of an activating reagent;
• wherein
• R1 is —CN or —C(O)NH2;
• Y is C1-C12 alkylene or C1-C12 alkenylene;
• R8 is C1-C12 alkyl;
• and
• R9 is hydrogen or C1-C12 alkyl.

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—NH2 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 C1-C12 alkylene or C1-C12 alkenylene;
• and
• R8 is C1-C12 alkyl.

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—NH2 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 NaHCO3 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 NaHCO3;
• 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 C1-C12 alkylene or C1-C12 alkenylene;
• and
• R8 is C1-C12 alkyl.

A process of preparing a compound having structural Formula (IIIc1):

• comprising
• reacting HO—Y—C(O)—NHR8 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 C1-C12 alkylene;
• and
• R8 is C1-C12 alkyl.