The invention relates to synthesis of eribulin mesylate, in particular to a method for preparing an intermediate compound II ((1R, 2S, 3S, 4S, 5S, 6R, 11S, 14S, 17S, 19R, 21R, 23S, 25R, 26R, 27S, 31R, 34S)-25-[(2S)-2, 3-dihydroxy]-2, 5-dihydroxy-26-methoxy-19-methyl-13, 20-dimethylene-24, 35, 36, 37, 38, 39-hexaoxaheptacyclo [29.3.1.13, 6.14, 34.111, 14.117, 21.023, 27] nonatriacontane-8, 29-diketone) of eribulin mesylate, which aims to solve the problem of low reaction yield of a traditional synthesis route.