Despite the pressure from regulatory authorities, DMF continues to play an important role in organic synthesis, along with other dipolar protic solvents including dimethylacetamide (DMAc) and N-methyl-2-pyrrolidone (NMP), all classified as CMR.
It is challenging for the pharmaceutical industry to avoid the use of this solvent. DMF is an effective solvent and can be difficult to replace in a chemical synthesis where the impurity profile and yield are crucial to the success of the process. Nonetheless, it is widely agreed that effort should be invested to avoid/limit the use of DMF where possible to achieve more sustainable chemistry.
Pharmaceutical manufacturing processes can run for 10-15 years (or longer), therefore solvent selection is important when considering the change in the regulatory landscape and trend towards green chemistry.
Recently, more sustainable and less harmful alternative dipolar aprotic solvents including DMSO, DMC, GVL, NBP and Propylene carbonate have gained increasing interest.