5-溴-2-甲基吡啶(2)经间氯过氧苯甲酸氧化得5-溴-2-甲基吡啶-1-氧化物(3);3与三氟乙酸酐反应后,经水解、游离得5-溴-2-羟甲基吡啶(6),收率由50%提高至68%;6再经氯代、磷酸酯化、成盐得[(5-溴吡啶-2-基)甲基]磷酸二乙酯盐酸盐(8),收率由89%提高至93%;8与3-氟苯硼酸(9)在四三苯基膦钯催化下进行Suzuki偶联,并通过成盐酸盐纯化得抗血栓药沃拉帕沙的关键中间体[[5-(3-氟苯基)吡啶-2-基]甲基]膦酸二乙酯盐酸盐(1),总收率46.4%(以2计),纯度99.15%。 5-Bromo-2-methylpyridine (2) was oxidized by chloroperbenzoic acid to give 5-bromo-2-methylpyridine 1-oxide (3); 3 After reaction with trifluoroacetic anhydride, , Yield 5-bromo-2-hydroxymethylpyridine (6), yield increased from 50% to 68%; 6 and then chlorinated, phosphorylated to salt [[5-bromopyridin- ) Methyl] phosphate diethyl ester hydrochloride (8), the yield increased from 89% to 93%; 8 and 3-fluorobenzeneboronic acid (9) were subjected to Suzuki coupling with tetrakistriphenylphosphine palladium The diethyl [(5- fluorophenyl) pyridin-2-yl] methyl] phosphonate hydrochloride (1), a key intermediate of the antithrombotic drug, The total yield of 46.4% (2), the purity of 99.15%.