Having established the important role of dissolved oxygen in promoting formation of dimer 6, we sought to directly measure* and identify an upper maximum limit for dissolved oxygen. Three one-liter-scale experiments were completed in order to assess the efficiency and feasibility of deoxygenation using subsurface sparging.
In these experiments, a mixture of water and 1-propanol was saturated with oxygen by subsurface addition of air, resulting in measurement of 8.3, 8.7, and 8.6 ppm oxygen. Nitrogen gas was then introduced at a rate of 0.5 standard cubic feet per hour (SCFH) resulting in reduction of dissolved oxygen to less than 0.5 ppm in 2.5 min. Thus, at 0.5 SCFH for 2.5 min, a total of 0.02083 standard cubic feet (SCF) of nitrogen was required to deoxygenate 1 L of solution. On this basis, we calculated that for 1000 L of reaction a purge rate of 30 SCFH of nitrogen for 41.7 min would be required to reduce the oxygen level from saturation to less than 0.5 ppm. Measurement of the recovered solution volume indicated that solvent loss due to evaporation was approximately 0.8%. We concluded that deoxygenation via subsurface sparging would be efficient and practical for large-scale work.
*An ICM model 31250 dissolved oxygen probe and meter was used for laboratory work. Devices such as Metler-Toledo InPro 6800/6900 or InPro 6800 Gas may be found more suitable for manufacture of clinical material.Ultimately, the authors end up doing this in their sub-kilo reaction (5.8 L solvent, 800 grams of SM) and getting a 93% yield. The concerns that I see with doing subsurface sparges of nitrogen on scale (apart from the loss of solvent from evaporation (problem should not scale?)) is the possibility of aerosolizing material and losing it to upper parts of the reactor.
Nevertheless, a really basic question answered nicely. (There's even a procedure for the experiment!)
 Miller, W.D.*; Fray, A.H.; Quatroche, J.T.; Sturgill, C.D. "Suppression of a Palladium-Mediated Homocoupling in a Suzuki Cross-Coupling Reaction. Development of an Impurity Control Strategy Supporting Synthesis of LY451395." Org. Process Res. Dev. 2007, 11, 359-364.