Novel and Efficient Synthesis of gem-Difluorinated Derivatives of Acyclic Nucleoside Phosphonates (ANPs)

0469886 - ÚOCHB 2017 RIV DE eng J - Journal Article
Pomeisl, Karel - Beier, Petr - Pohl, Radek - Krečmerová, Marcela
Novel and Efficient Synthesis of gem-Difluorinated Derivatives of Acyclic Nucleoside Phosphonates (ANPs).
ChemistrySelect. Roč. 1, č. 10 (2016), s. 2102-2106. ISSN 2365-6549. E-ISSN 2365-6549
R&D Projects: GA ČR(CZ) GA14-00522S
Institutional support: RVO:61388963
Keywords : difluoromethylation * difluoromethylphosphonate * acyclic nucleoside phosphonate * phosphonate ester * microwave reaction
Subject RIV: CC - Organic Chemistry

A novel efficient method for the synthesis of gem-difluorinated derivatives of acyclic nucleotide analogues has been developed. The method is based on utilization of diethyl difluoromethylphosphonate as a nucleophilic difluoromethylation reagent. In contrast to previous difluoromethylation procedures using commercially available DAST or deoxofluor, this process is very robust, proceeds under mild conditions and is accompanied only by small amounts of by-products. The reaction of diethyl difluoromethylphosphonate with 2-benzyloxyacetaldehyde afforded 3-(benzyloxy)-1,1-difluoropropan-2-ol (6) a key precursor for syntheses of difluoromethylated analogues of various acyclic nucleoside phosphonates.
Permanent Link: http://hdl.handle.net/11104/0267657