2-Bromohexadecanoic acid → 2-chlorohexadecanoic Acid

To 2-bromohexadecanoic acid (1 g), after having been dissolved in acetonitrile (50 ml), were added calcium chloride (5 g) and tetramethylammonium chloride (1 g), and the mixture was heated under reflux for 6 hours. The reaction mixture was filtered, concentrated and distributed into chloroform and water, and the chloroform layer was dried over anhydrous sodium sulfate and concentrated to give 2-chlorohexadecanoic acid (0.80 g). 2-Chlorohexadecanoic acid (893 mg), para-nitrophenol (428 mg) and N,N'-dicyclohexylcarbodiimide (634 mg) were dissolved in N,N-dimethylformamide (DMF), and the mixture was stirred for 12 hours. Precipitates were removed by filtration, and DMF was removed by distillation to give the active ester of 2-chlorohexadecanoic acid. To the active ester, which was dissolved in DMF (500 mg), were added again 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (465 mg) and triethylamine (1.2 ml), and the mixture was stirred for 12 hours. The reaction mixture was concentrated, and the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK135 in the yield of 262 mg.

1. temperaturethe mixture was heated
2. temperatureunder reflux for 6 hours
3. filtrationThe reaction mixture was filtered
4. concentrationconcentrated
5. dry with materialthe chloroform layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated

ORD record

ord-84282fa69ec44722946a77893a98155f

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05631238