12-Bromododecanoic Acid → 12-Chloro-dodecanoic acid

Participants

Reaction Steps

To 12-bromododecanoic acid (1 g) dissolved in acetonitrile (50 ml) was added calcium chloride (2 g) and tetra-n-butylammonium chloride (1.2 g), and the mixture was heated under reflux for 4 hours. The reaction mixture was filtered, concentrated and distributed into ethyl acetate-water, and the ethyl acetate layer was dried over anhydrous sodium sulfate to give 12-chlorododecanoic acid. After a 280 mg portion of 12-chlorododecanoic acid thus obtained, para-nitrophenol (167 mg) and N,N'-dicyclohexylcarbodiimide (245 mg) in N,N-dimethylformamide (DMF) was stirred for 12 hours, precipitates were removed by filtration and DMF was removed by distillation to give an active ester. To the active ester of 12-chlorododecanoic acid dissolved in DMF were added 6- (4'-N-glycyl-spicaminyl-amino)purine hydrochloride (456 mg) and triethylamine (1.2 ml), and the mixture was stirred for 12 hours. The reaction mixture was concentrated and subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK132 in the yield of 287 mg.

Provenance & Evidence