Abstract: A simple and efficient synthesis optimization method for two proline organocatalysts based on the application of LC-MS/MS was reported. We not only found the best synthetic conditions for proline organocatalysts, but also figured out the different effects of each individual factor. The synthetic products could be well isolated from the reagents based on the optimized HPLC method. At the same time, by taking advantage of the strong structure illustration ability of tandem mass spectrometry, we were able to identify the molecular structure of the proline organocatalysts and further understand the related synthetic mechanisms. The method we established found the best synthetic conditions for proline organocatalysts and identified the products and their purities rapidly and accurately. It was a time-saving, economical and effective research method and analytical tool, which could be used for monitoring organic reactions and identifying their products.