Patent ID: 8431693

Claim:
A process comprising the steps of: a) synthesizing a nucleic acid molecule comprising one or more nucleotides, using a method selected from the group consisting of solid phase phosphoramidite, solution phase phosphoramidite, solid phase H-phosphonate, solution phase H-phosphonate, hybrid phase phosphoramidite, and hybrid phase H-phosphonate-based synthetic methods; b) contacting said nucleic acid molecule from step (a) with aqueous alkylamine; ammonia; a low-volatility amino compound selected from the group consisting of polyamine, PEHA, PEG-NH 2 , short PEG-NH 2 , cycloalkyl amine, hydroxycycloalkyl amine, hydroxyamine, thioalkylamine, thiolated amine, β-amino-ethyl-sulfonic acid or a sodium sulfate thereof, and combinations thereof; or combinations thereof, under conditions suitable for the removal of any 2′-amino protecting groups, exocyclic amino (base) protecting groups and/or phosphate protecting groups from said molecule; c) contacting reaction mixture having said nucleic acid molecule from step (b) with pyridine-HF, DMAP-HF (dimethylaminopyridine-HF), urea-HF, TASF (tris(dimethylamino)sulfonium difluorotrimethylsilane), DAST (diethylaminosulfur trifluoride), polyvinyl pyridine-HF or an amine-HF reagent of formula AA and a polar solvent selected from the group consisting of DMSO, DMF, ethanol, isopropanol, methanol, acetonitrile, and combinations thereof, under aqueous conditions for the removal of a silyl protecting group and/or a 2′-OH protecting group, wherein R 1 is alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl; R 2 is alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl; R 3 is aryl or heteroaryl; and n is 1 to 20; d) loading reaction mixture having said nucleic acid molecule from step (c) onto a chromatography media in a suitable buffer; and e) applying a purification gradient using a suitable elution buffer, and pooling and desalting the pure fractions.