Alternative to Dichloromethane

05 March 2004

Methyltetrahydrofuran has been shown to be a superior solvent to DCM in two-phase reactions. MeTHF is a non-reactive solvent with a boiling point of 78-80°C and forms an effective azeotrope with water (72°C, 1.9% water). For example simple acylations of amines can be carried out in a 2-phase process to give high yields of amides (Brown-Ripin et al, SynLett, 2003, 2353).

In a study aimed at an improved manufacturing method for Atorvastatin (Lipitor), the key Paal-Knorr process was examined in a range of solvents. MeTHF turned out to be one of the best - trifluorotoluene was slightly better. (J Zeller, Pfizer, presented at Chiral USA, Chicago, 2003).