HCID 22825315, compound → 4-Hydroxy-L-lysine

Participants

Reaction Steps

N,N'-Dicarbobenzyloxy-γ-hydroxy-L-lysine amide (2.0 g, 4.65 mmol) (described by Izumiya et al., Biochem, 4, 2501 (1965)) was placed in a Kel-F® reactor and anhydrous hydrogen fluoride (40 ml) was condensed at -78° C. Sulfur tetrafluoride (1.8 ml, 31 mmol) was condensed at -78° C. in a graduated tube attached to the reaction vessel. The cooling bath was removed and sulfur tetrafluoride was transferred into the reaction solution (cooled at -78° C.) by evaporation. The mixture was stirred at -78° C. for 5 hours and allowed to stand overnight. Hydrogen fluoride was removed by a stream of nitrogen and the residue dissolved in 30 ml of 2.5 N HCl. Insoluble material was filtered and the filtrate evaporated to dryness in vacuo to yield 1.01 g of crude 4-fluoro-L-lysine amide contaminated with unreacted 4-hydroxy-L-lysine amide. The crude amide (1.4 g) was hydrolyzed in 90 ml 2.5 N HCl by refluxing for 1.5 hours, the reaction solution was evaporated to dryness and separated by ion exchange chromatography (Dowex 50-X8 resin, 120 ml, H+ form, washed first with 500 ml water and eluted with 2.5 N HCl). The 4-hydroxy-L-lysine in strong acid formed the lactone which, being a strong base, was not eluted from the resin with 2.5 N HCl. 4-Fluoro-L-lysine.2HCl was obtained in 52% yield and >90% purity, [α]D25 +16.8° (3% in 2.5 N HCl. The monohydrochloride was obtained in 76% yield by dissolving the dihydrochloride in 15 volumes methanol and adding 50% molar excess pyridine. This material was recrystallized from isopropanol/water (2:1) to give a product with a rotation of [α]D25 +25° (2% in 2.5 N HCl) mp: 210° (discoloration), 215°-17° (d).

Provenance & Evidence