67396-08-1

67-56-1

657-27-2

13515-95-2

L-lysine hydrochloride (2, 5.00 g, 27.4 mmol, 1.0 eq.) and methanol (30 mL, 0.9 M) were added to a round bottom flask. The suspension was heated to reflux to completely dissolve the solid. Thionyl chloride (2.59 mL, 35.6 mmol, 1.3 eq.) was added slowly and dropwise over 15 min. The reaction mixture was kept under reflux conditions for 17 hours. Removal of most of the volatiles (~25 mL) by distillation followed by azeotropic removal of the remaining volatiles by toluene under reduced pressure afforded pure lysine methyl ester dihydrochloride (3, quantitative mass recovery, white solid), which was used directly in the next step of the reaction without further purification. The product was analyzed and the data were consistent with those reported in the literature.