We applied process analytical technologies to solve the problem of selectivity in the hydrogenation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride (1) to (±)3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride (2). We showed that both mid-IR and near-IR (NIR) were suitable for in-line analysis of the hydrogenation. We chose to use NIR in the production environment due to easier implementation. We developed a NIR model by correlation of NIR results with HPLC results for a laboratory-scale hydrogenation reactor, and we used production batch data to adjust and confirm this model.

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