89268-01-9Relevant articles and documents
Synthesis of Rovafovir Etalafenamide (Part III): Evolution of the Synthetic Process to the Phosphonamidate Fragment
Ambrosi, Andrea,Bringley, Dustin A.,Calimsiz, Selcuk,Curl, Jonah,Garber, Jeffrey A. O.,Huynh, Huy,Kwong, Bernard,Lapina, Olga,Leung, Edmund,Lin, Lennie,Martins, Andrew,McGinitie, Teague,Mohan, Sankar,Phull, Jaspal,Roberts, Ben,Rosario, Mary,Sarma, Keshab,Shen, Jinyu,Shi, Bing,Standley, Eric A.,Wang, Li,Wang, Xueqing,Yu, Guojun
supporting information, p. 1247 - 1262 (2021/05/29)
Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography for the separation of phosphorus diastereomers, was executed on scale to produce multiple batches of 1. However, developing alternative synthetic conditions became desirable in consideration of the high production cost, long lead time, and high process mass intensity (PMI) associated with SMB. Several strategies to improve these factors are described herein, including epimerization and recycling of the undesired (R)-phosphorus diastereomer, design of stereoselective approaches to establish the desired (S)-configuration at phosphorus, and identification of conditions or derivatives to allow for selective crystallization. Ultimately, a second-generation route to 1 was developed and demonstrated on scale. The new route achieves the separation of phosphorus diastereomers by means of selective crystallization, does not require SMB, and offers lower PMI, cost, and lead time.
Dynamic kinetic resolution based asymmetric transfer hydrogenation of α-alkoxy-β-ketophosphonates. Diastereo- and enantioselective synthesis of monoprotected 1,2-dihydroxyphosphonates
Son, Se-Mi,Lee, Hyeon-Kyu
, p. 2666 - 2681 (2014/04/17)
Dynamic kinetic resolution driven, asymmetric transfer hydrogenation reactions of a wide range of 2-substituted α-alkoxy-β- ketophosphonates 3 were observed to proceed efficiently to give the corresponding 2-substituted α-alkoxy-β-hydroxy phosphonates 4 w
A Convenient One-pot Synthesis of Polyenic Enol Ethers
Vo-Quang, Yen,Carniato, Denis,Vo-Quang Liliane,Goffic, Francois Le
, p. 1505 - 1506 (2007/10/02)
Diethyl alkoxymethylphosphonates react with unsaturated aldehydes to give polyenic enol ethers with a good stereoselectivity.
