Yield:-

Reaction Conditions:

with thionyl chloride in dichloromethane at 20; for 2.5 h;Heating / reflux;

Steps:

13

A mixture of 6-hydroxynicotinic acid (1.4 g), thionylchloride (1.1 ml) and dichloromethane (25 ml) was refluxed for 2 hours to form a clear solution. After evaporation the residue was evaporated twice from toluene, redissolved in dichloromethane with stirring and cooled in ice. A solution of ethanolamine (5 ml) in dichloromethane (20 ml) was added dropwise during 30 minutes followed by stirring for 2 hours at room temperature. Water was added and after extraction three times with dichloromethane, the aqueous phase was freeze-dried. The crude product was purified by chromatography on silica gel with ethyl acetate/ methanol/aqueous ammonia as eluent. Fractions containing the title compound were evaporated and the product crystallised from acetone.¹H NMR (DMSO) δ =11.80 (bs, OH), 8.20 (t, NH), 7.99 (d, IH), 7.86 (dd,lH), 6.34 (d,lH), 4.70 (bs, OH), 3.47 (t,2H), 3.26 (q,2H)

References:

WO2006/66584,2006,A1 Location in patent:Page/Page column 20