Processes for preparing 6-hydroxy-3,4-dihydroquinolinone, cilostazol and N-(4-methoxyphenyl)3-chloropropionamide

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising the steps of

• adding p-anisidine and from about 1 to 1.2 equivalents of triethylamine, with respect to the p-anisidine, to methyl ethyl ketone,
• adding from about 0.9 to about 1.1 equivalents of 3-chloropropionyl chloride,
• heating the resulting mixture to reflux temperature,
• precipitating a solid from the reaction mixture and
• washing the solid with water, wherein the washed solid is N-(4-methoxyphenyl)-3-chloropropionamide in greater than 98% purity, and
• wherein the purity is obtained without requiring recrystallizing the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising the steps of

• dissolving p-anisidine in dichloromethane to form a solution,
• adding from about 0.9 to about 1.1 equivalents of 3-chloropropionyl chloride and from about 0.9 to about 1.1 equivalents sodium hydroxide at a temperature of 0° C. or less in a manner that maintains approximately neutral pH in the (4-methoxyphenyl)-3-chloropropionamide solution, thereby precipitating a solid, and
• washing the solid with water, wherein the washed solid is N-(4-methoxyphenyl)-3-chloropropionamide in greater than 98% purity, and
• wherein the purity is obtained without requiring recrystallizing the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising the steps of

• dissolving p-anisidine in N,N-dimethylformamide,
• adding from about 0.9 to about 1.1 equivalents 3-chloropropionyl chloride, with respect to the p-anisidine, to the solution,
• allowing, for a sufficient time and temperature, to form N-(4-methoxyphenyl)-3-chloropropionamide,
• adding water to the mixture, thereby precipitating a solid, and
• washing the solid with water, wherein the washed solid is N-(4-methoxyphenyl)-3-chloropropionamide in greater than 98% purity, and
• wherein the purity is obtained without requiring recrystallizing the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising:

• admixing p-anisidine, sodium bicarbonate, and toluene to form an admixture;
• adding 3-chloropropionyl chloride to the admixture;
• maintaining the admixture at a temperature for a sufficient time to form N-(4-methoxyphenyl)-3-chloropropionamide;
• and
• recovering the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising:

• admixing p-anisidine, triethylamine, and methyl ethyl ketone to form an admixture;
• adding 3-chloropropionyl chloride to the admixture;
• maintaining the admixture at a temperature for a sufficient time to form N-(4-methoxyphenyl)-3-chloropropionamide;
• and
• recovering the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising:

• admixing p-anisidine and dichloromethane to form an admixture;
• adding 3-chloropropionyl chloride and sodium hydroxide to the admixture at a temperature of 0° C. or less in a concerted manner that maintains approximately neutral pH in the admixture, thereby forming N-(4-methoxyphenyl)-3-chloropropionamide;
• and
• recovering the N-(4-methoxyphenyl)-3-chloropropionamide.

A process for preparing N-(4-methoxyphenyl)-3-chloropropionamide comprising:

• admixing p-anisidine and N,N-dimethylformamide,
• adding 3-chloropropionyl chloride to the admixture;
• maintaining the admixture at a temperature for a sufficient time to form N-(4-methoxyphenyl)-3-chloropropionamide;
• and
• recovering the N-(4-methoxyphenyl)-3-chloropropionamide.