To cope with the difficulties in synthesizing operating procedures for the process with complicated operational constraints, a two-tier planning methodology is presented in this paper in which the top-tier determines the operating path using optimization methods, and the bottom-tier synthesizes the primitive operations through a model based reasoning which is generic. The methodology is suitable for quantitative planning of operating procedures when operational constraints are more stringent. A case study is given to illustrate how the methodology is used in a case containing complex mixing constraints.