Using Phase Transfer Catalysis In Borohydride Reductions

A recent article in Phase Transfer Catalysis communications (issue No. 15 p4 - see www.phasetransfer.com for subscription information) quotes an excellent example about process efficiency. The example comes from a patent (Magni A, 1989 Eur Pat EP 0346765) by Gruppo Lepetit for a process to make terfenadine, in which the last step is a reduction of an aromatic ketone to an alcohol by borohydride. This reaction works well in ethanol, but when the terfenadine is crystallised from ethanol, it gives the wrong polymorph, so a further, wasteful crystallisation from xylene has to be carried out. By doing the borohydride reduction in a water-xylene two phase system with a PTC catalyst, methyltributylammonium chloride, a one step process yielding the correct form of terfenadine in 97.7% yield was developed. In addition, the amount of borohydride was reduced from 30 mole % to 4 mole %.