ONLINE DETERMINATION OF REACTION COMPLETION IN A CLOSED-LOOP HYDROGENATOR USING NIR SPECTROSCOPY

An on-line near-infrared (NIR) spectroscopic method has been developed to determine iii situ the endpoint of a bulk pharmaceutical hydrogena tion reaction in a loop hydrogenator, This hydrogenation employs a 5% palladium-on-carbon catalyst with tetrahydrofuran (THF) as the reactio n solvent, The traditional test for monitoring the endpoint of the hyd rogenation is a gas chromatographic procedure that requires an estimat ed 60 min from the time a sample is taken to the point where the analy sis results become available. The use of NIR spectroscopy in an on-lin e mode of operation allows spectra to be collected every 2 min and the reby significantly improves response time and result availability. The need for obtaining results in ''real time'' stems from the creation o f undesired side products if the reaction is allowed to continue past the optimal endpoint. If the reaction is not stopped before these side products reach a level of approximately 0.8% (wt/wt), the batch requi res additional purification at considerable time and cost. A partial l east-squares model was constructed, validated, and successfully used t o determine the endpoint of subsequent batches.