Acetic acid, 2-(triphenylphosphoranylidene)-, methyl ester → Hexadecadienoic Acid

To the trans-2-tetradecenal (2.3 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (4.4 g), and the mixture was stirred for 2 hours. The reaction mixture was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans,trans-2,4-hexadecadienoic acid (2.2 g). Potassium hydroxide (2.8 g) was dissolved in a mixed solvent of ethanol-water (1:1), and the methyl ester of trans,trans-2,4-hexadecadienoic acid (2.2 g). After the mixture was stirred at 60° C. for 40 minutes, it was cooled, adjusted to a weak acidic range of pH with citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give trans,trans-2,4-hexadecadienoic acid (2.0 g). The product was dissolved in N,N-dimethylformamide (DMF, 50 ml), and para-nitrophenol (1.1 g) and N,N'-dicyclohexylcarbodiimide (1.6 g) were added. The mixture was stirred for 12 hours. After the reaction, precipitates produced were removed by filtration, DMF was removed by distillation, and the residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 200:1 to 50:1) to give the active ester of trans,trans-2,4-hexadecadienoic acid (0.8 g). To the active ester (340 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (500 mg) and triethylamine (1.2 ml). The mixture was stirred for 12 hours. After the solvent was removed by distillation, 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 SPK283 in the yield of 270 mg.

ORD 기록

ord-1a519f79617f4944a520ab69770286f8

출처 데이터셋

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05631238