The invention discloses a one-pot synthesis method of a flomoxef intermediate. According to the existing method, problems that reaction steps are multiple, post-processing is complicated, metal is remained in products exist. The synthesis method comprises the following steps of: taking 7 alpha-methoxy-7 beta-acylamino-3-chloromethyl-oxacephem as a starting material; and sequentially carrying out five steps of chloro, alcoholysis, hydrolysis, acylation and substitution in organic solvent to prepare the flomoxef intermediate through the one-pot synthesis method. The one-pot synthesis method has moderate reaction conditions and high product yield and purity, groups in the side chains have no need to be protected, the reaction steps are reduced, and the induction of metal impurities in deprotection reaction is avoided.