To ensure successful scale-up for a prodrug of ABT-199, the key alkylation step was optimized, and the mechanism was explored. The use of 1,8-bis­(dimethylamino)­naphthalene was essential for high conversion and selectivity, and statistical experimental design yielded the optimal stoichiometries to maximize the yield and minimize impurities. Kinetic interrogation demonstrated that the rate-determining step was phosphate activation and not alkylation as might be presumed, and evidence for a radical chain mechanism was uncovered. Further support for a radical chain mechanism was found in a novel solvent-based linear free energy relationship between the Hansen solubility parameters and the observed rate. The level of mechanistic understanding informed successful scale up to 1, 10, and 20 kg.