2′,3′,5′-Tri-O-acetyl-6-chloropurine nucleoside was obtained from inosine via acetylation and chlorination. Then, 2′,3′,5′-tri-O-acetyl-6-chloropurine nucleoside was transformed into 2′,3′,5′-tri-O-acetyl-6-triphenylphosphonine nucleoside with triphenylphosphine. Finally, C—P bond was cleavaged in the presence of K2CO3, and acetyl groups were removed simultaneously. The product Nebularine was obtained in 4 steps and 62% overall yield. The effects of the formation and cleavage of C—P bond on the yields were investigated, and the optimized reaction conditions were obtained. The reaction scale could be expanded to 200 g. 6-Deuterated Nebularine was obtained in 76% yield from 2′,3′,5′-tri-O-acetyl-6-triphenylphosphonine nucleoside in deuterated water and deuterated methanol.