Transmission infrared in situ measurement technique was used to assess its feasibility for real-time process analysis. In particular, the advanced chemometric analysis by band- target entropy minimization (BTEM) was implemented to obtain pure component spectral estimates from the multicomponent reaction system. In this case study, the rhodium-catalyzed reductive amination of 1-decanal in thermomorphic multiphase systems was investigated. This complex reaction/separation approach consisted of more than 10 IR-active components so that the herein-implemented BTEM technique, built for improved data handling, was highly challenged. Seven parameters with significant impact on the BTEM algorithm were identified and investigated regarding the general resolution quality of each spectral estimate. Herein, the BTEM algorithm was extended with an automatic band-target selection and parameter limits regarding the Savitzki-Golay filter for tuning raw data. Finally, the source code of the algorithm for MATLAB is published to find use in extended spectroscopic applications.