Why are the yields lower for modified bases?
Many of the modified amidites are unstable and do not couple as efficiently as the unmodified bases (even though longer coupling procedures may be used), thus failure sequences are more abundant than in normal synthesis. Consequently, all modified oligos should be purified either by cartridge or HPLC to remove the more abundant failure sequences. Yields are reduced as a result of purification.. The end product, although with a lower yield, is much more pure.