13086-84-5Relevant articles and documents
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Cherbuliez,E. et al.
, p. 1653 - 1659 (1964)
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Kosolapoff
, p. 4953 (1952)
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Di- tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir
Dietz, Jule-Philipp,Ferenc, Dorota,Jamison, Timothy F.,Gupton, B. Frank,Opatz, Till
, p. 789 - 798 (2021/03/01)
Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OtBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The developed protocol could also be applied for the preparation of the hepatitis B drug adefovir (64% yield/1 g scale).
Development of efficient processes for the preparation of Di-tert-butyl potassium phosphate and Di-tert-butyl (Chloromethyl) phosphate
Zheng, Bin,Fox, Richard J.,Sugiyama, Masano,Fritz, Alan,Eastgate, Martin D.
, p. 636 - 642 (2014/06/09)
A new and efficient process to prepare di-tert-butyl (chloromethyl) phosphate, a key compound in the formation of many phosphon-oxymethyl pro-drugs, from chloromethyl chlorosulfate (CMCS) and di-tert-butyl potassium phosphate (DTBPP) is described. To develop a process to this important compound with overall efficiency, an improved synthesis of DTBPP was required. The two-step process to DTBPP starts from PCl3 and leverages a H2O 2/catalytic KI mediated oxidation of di-tert-butyl phosphite to provide DTBPP in 81% yield and high purity. In the development of the new process to di-tert-butyl (chloromethyl) phosphate, a comparison to the corresponding tosylate derivative was made. A rational selection of base, phase-transfer catalyst (PTC), and stabilizing additive minimized CMCS decomposition and led to an optimized yield (90% solution yield), improved product purity, and identification of a technique to enable the long-term storage of di-tert-butyl (chloromethyl) phosphate.
Thermal Retro-Trimerization of Some 1,3,5,2,4,6-Trioxatriphosphorinanes to Phosphenites
Quin, Louis D.,Ionkin, Alexey S.
, p. 5186 - 5189 (2007/10/02)
Pyrolysis in a packed tube of the vapor from three 2,4,6-tris(aryloxy)-1,3,5,2,4,6-trioxatriphosphorinanes was performed at 300-350 deg C and 1E-6 mm; the product was collected on a cold finger chilled by liquid nitrogen.The cracking of the trimer was complete, and the product at -195 deg C appeared to consist only of the monomeric aryl phosphenite, ArOP=O.On warming, dimerization occured, later followed by trimer formation.The weak 31P NMR signal for the phosphenite (about δ 238 for three O-aryl derivatives) persisted in the solution for several weeks if water was rigorously excluded.Treatment of the phosphenite with water or alcohols at -195 deg C gave a mixture of products; the major product (ArO-PH(O)OH) came from addition of the nucleophile to the P=O bond, but significant amounts (10-20percent) of dialkyl H-phosphonates (HP(O)(OR)2) were present, apparently from displacement of the O-aryl substituent of the phosphenite, followed by addition to the double bond.
