Hydrochloric Acid → 2-CYCLOPROPYLAMINONICOTINIC ACID

Participants

Reaction Steps

A 45% aqueous KOH solution (187g, 1.5 mol) was charged to a mixture of the product from Example 1 and 300 ml of 1-propanol. The mixture was heated at reflux temperature for about 5 hours whereupon TLC analysis showed complete hydrolysis of the nitrile. The reaction mixture was cooled to ambient temperature and treated with 94 g of water that was needed to remove the 1-propanol by azeotropic distillation. About 330 g of water/1-propanol azeotrope was distilled off at 62° C. and 21.1 in. Hg. Water (130 g) was added to the reaction mixture and the mixture chilled to 5-10° C. Concentrated hydrochloric acid (148 g, 1.5 mol) was added at such a rate that the temperature could be maintained below 30° C. After about 80-90% of the acid was added the zwitterion began to precipitate out, making the mixture quite thick. When all the acid had been added, the solid product was collected by filtration, using 90 ml of cold water to rinse out the reaction vessel onto the filter cake. The product was dried to yield 68.12 g. of the zwitterion.

Provenance & Evidence