3084-40-0Relevant articles and documents
An efficient and simple strategy toward the synthesis of highly functionalized compounds
Jmai, Momtez,Efrit, Mohamed Lotfi,Dubreuil, Didier,Blot, Virginie,Lebreton, Jacques,M'rabet, Hédi
, p. 978 - 995 (2021/08/06)
The expedient syntheses of small libraries of ((β-ethoxycarbonyl, -cyano and -acetyl)propyloxy) methylphosphonate scaffolds bearing olefin, sulfanyl, or amine functions are described. All these new derivatives are readily produced from easily available starting reagents (aldehydes, electron-poor olefins, and dialkylphosphites) following a three steps reaction sequence of condensations, SN2′-type reaction and a conjugated thia- or aza-Michael 1,4-addition with aromatic and aliphatic thiol or amine nucleophiles.
Preparation method of diethyl p-toluenesulfonyloxymethylphosphonate
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Paragraph 0092-0096; 0106-0109; 0115-0118, (2021/07/17)
The invention relates to a preparation method of diethyl p-toluenesulfonyloxymethylphosphonate. The method comprises the following steps of under the protection of nitrogen, adding diethyl phosphite into a reaction container, then sequentially adding carbonate and tetrabutylammonium bromide, and dropwise adding a formaldehyde aqueous solution while stirring, continuously adding the carbonate and the formaldehyde aqueous solution in batches, after the reaction endpoint is reached, adding methylbenzene, adding paratoluensulfonyl chloride while stirring, and reacting, dropwise adding an alkali solution, after dropwise adding, keeping the temperature until the reaction end point, and standing, separating liquid, placing an upper-layer organic phase for later use, and extracting a lower-layer water phase with methylbenzene, and combining the two organic phases, adding a sodium chloride aqueous solution for washing, and concentrating an organic layer under reduced pressure to obtain a liquid product. Energy consumption does not need to be additionally increased in the reaction, so that frozen saline water required for cooling in the traditional process is abandoned, and the energy consumption is greatly reduced; compared with the traditional process with the step of about 85% of the yield, the yield is improved by 10-15%, the economic value of the product is greatly improved, and environmental protection is facilitated.
An improved synthesis of adefovir and related analogues
Jones, David J.,O’Leary, Eileen M.,O’Sullivan, Timothy P.
supporting information, p. 801 - 810 (2019/04/17)
An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach.
Synthesis method of diethyl (tosyloxy)methylphosphonate
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Paragraph 0027-0034, (2019/01/14)
The invention discloses a synthesis method of diethyl (tosyloxy)methylphosphonate. The method takes diethyl phosphite, paraformaldehyde, paratoluensulfonyl chloride, inorganic base and the like as rawmaterials, and the product is obtained by carrying out carrying out aftertreatment operations such as aqueous phase condensation, an esterification two-step reaction and layering. The method has thecharacteristics of being enough in raw materials source, low in price, high in safety of synthetic process, high in product yield, less in pollution caused by three wastes, environmentally-friendly, and the like, thus having a higher industrial value.
Preparation method of adefovir dipivoxil crystals
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Paragraph 0017-0019, (2017/07/21)
The invention belongs to the technical field of drug preparation and in particular relates to a preparation method of adefovir dipivoxil crystals. The preparation method comprises the following steps: synthesizing diethyl phosphite; synthesizing diethyl (p-phenylsulfonyloxy)methylphosphonate; synthesizing 9-(2-hydroxyethyl) adenine; synthesizing 4,9-[2-(diethylphosphonomethoxy)ethyl]adenine; synthesizing adefovir; synthesizing adefovir dipivoxil. Compared with the prior art, the preparation method of the adefovir dipivoxil crystals, provided by the invention, takes acetonitrile as a water-soluble organic medium, and the difficulty that DMF (Dimethyl Formamide) is difficult to remove is overcome; ethyl acetate is used for replacing isopropyl acetate in a previous process, isopropyl ether is used for replacing ethyl ether and ethanol is used for replacing acetone; the preparation method is simple to operate; the obtained product has good purity and high yield; the industrialized production is easy to realize and the production cost is reduced.
Method of preparing tenofovir
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Paragraph 0055; 0056; 0057, (2017/08/25)
The invention provides a method for preparing tenofovir. The method is characterized by comprising the following steps: 1) reacting 9-(2-hydroxy propyl) adenine with a compound as shown in the formula (1) in the specification in the presence of magnesium alkoxide to prepare tenofovir ethyl ester, wherein Y is selected from methyl, trifluoromethyl, phenyl or 4-trifluoromethylphenyl; 2) hydrolyzing the tenofovir ethyl ester in the presence of a dealkylation reagent to prepare tenofovir. The method for preparing tenofovir provided by the invention has the advantages of safe process, good product quality, high yield and suitability for industrialization.
Wittig–Horner mediated synthesis of 4-vinyl sulfide derivatives of pyrazoles
Padilha, Gustavo,Kaufman, Teodoro S.,Silveira, Claudio C.
, p. 3349 - 3353 (2016/07/12)
The synthesis of a series of 4-vinyl sulfide derivatives of 1,3-diarylpyrazoles, including their corresponding sulfoxides and sulfones, is reported. Access to the target vinyl sulfides was stereoselectively achieved, in moderate to good yields, by the n-BuLi-mediated Wittig–Horner reaction of 4-formylpyrazoles with arylthiophosphonates and α-chloroarylthiophosphonates in dimethoxyethane. Their oxidation with H2O2in AcOH and mCPBA in CH2Cl2afforded satisfactory yields of the expected vinyl sulfoxides and vinyl sulfones, respectively. Enrichment in the more stable isomers during both oxidation processes was detected and a plausible general mechanistic explanation was given to these observations.
Method of preparing tenofovir
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Paragraph 0051; 0052, (2017/02/02)
The invention provides a method for preparing tenofovir. The method is characterized by comprising the following steps: 1) reacting 9-(2-hydroxy propyl) adenine with p-fluorobenzenesulfonyl diethyl methylphosphonite in the presence of magnesium alkoxide to prepare tenofovir ethyl ester; 2) hydrolyzing the tenofovir ethyl ester in the presence of a dealkylation reagent to prepare tenofovir. The method for preparing tenofovir provided by the invention has the advantages of safe process, good product quality, high yield and suitability for industrialization.
Diethyl p-toluenesulfonyloxy methylphosphonate synthesis method
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Paragraph 0033, (2016/11/07)
The invention relates to the technical field of medicine, and specifically relates to a synthesis method of diethyl p-toluenesulfonyloxy methylphosphonate. The method comprises the following steps: (1) diethyl hydroxymethylphosphonate is synthesized, wherein diethyl phosphite, a solvent, a catalyst and paraformaldehyde are sequentially added into a reactor; heating is carried out and a reaction is allowed; filtering is carried out after the reaction; the solvent is removed through distillation, and the remaining substance is diethyl hydroxymethylphosphonate; and (2) diethyl p-toluenesulfonyloxy methylphosphonate is synthesized, wherein diethyl hydroxymethylphosphonate prepared in the step (1) is cooled; dichloromethane and p-toluenesulfonyl chloride are added; an acid binding agent is dropped in, and stirring is continuous for 1.5-2.5h after dropping; heating is carried out and a reaction is allowed; after the reaction, extraction, water washing and distillation are carried out, and the remaining substance is a crude product; and purification is carried out, such that a diethyl p-toluenesulfonyloxy methylphosphonate product is obtained. The method provided by the invention has the advantages of low energy consumption, simple product post treatment, high yield and high product purity. The yield can be higher than 80%. The purity can be higher than 99%.
Industrialization production technology for tenofovir disoproxil fumarate
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Paragraph 0012-0013, (2017/04/11)
The invention relates to an industrialization production technology for tenofovir disoproxil fumarate. The production technology comprises the following steps that firstly, R-1,2-polylene glycol, diethyl carbonate and sodium ethoxide are added into a reaction kettle; absolute ethyl alcohol and diethyl phosphite are added into the reaction kettle and stirred, paraformaldehyde and triethylamine are added after stirring is completed, after the complete reaction is achieved, anhydrous sodium sulfate is added, drying, filtering and steaming are carried out, and a steamed product is a diethyl p-toluenesulfonyloxymethylphosphonate fine product; adenine, R-propylene carbonate, DMF and NaOH are added into the reaction kettle, after the complete reaction is achieved, magnesium tert-butoxide is added, p-toluenesulfonyloxy phosphonate is dropwise added, after the complete reaction is achieved, acetic acid is added, vacuum concentration is carried out, hydrochloric acid is added, filtering is carried out, solids are filtered out and dried at the normal pressure, and a PMPA fine product is obtained. The industrialization production technology has the advantages of being high in yield and product purity, low in impurity content and capable of being completely applied to industrialization production.
