1445-75-6

Usage

Uses

1. Used in Chemical Synthesis:
DIISOPROPYL METHYLPHOSPHONATE is used as a precursor for the preparation of beta-keto phosphonates, which are essential intermediates in the synthesis of various organic compounds.
2. Used in Horner-Wadsworth-Emmons Olefination:
DIISOPROPYL METHYLPHOSPHONATE acts as an intermediate in the Horner-Wadsworth-Emmons olefination of carbonyl compounds. This reaction is a widely used method for the synthesis of alkenes, which are crucial building blocks in organic chemistry and have applications in pharmaceuticals, agrochemicals, and materials science.

InChI:InChI=1/C7H17O3P/c1-5(2)7(6(3)4)11(8,9)10/h5-7H,1-4H3,(H2,8,9,10)/p-2

Upstream product

• 74-83-9 methyl bromide 
• 116-17-6 triisopropyl phosphite 
• 676-97-1 methylphosphonic acid dichloroanhydride 
• 67-63-0 isopropyl alcohol 
• 14540-27-3 diisopropyl ethyl phosphite 
• 74-88-4 methyl iodide 
• 1445-76-7 methylphosphonic chloride isopropyl ester 
• 106-89-8 epichlorohydrin 
• 683-60-3 sodium isopropylate 
• 917-64-6 methyl magnesium iodide 
• 132213-27-5 3-(diisopropoxyphosphinoyl)-5-phenylisoxazole 
• 15267-38-6 thiophosphoric acid O,O'-diisopropyl ester S-phenyl ester 
• 917-54-4 methyllithium 
• 108-21-4 Isopropyl acetate 

Downstream Products

• 1445-76-7 methylphosphonic chloride isopropyl ester 
• 1832-54-8 methylphosphonic acid isopropyl ester 
• 146286-12-6 ((E)-2-Hydroxy-4-phenyl-but-3-enyl)-phosphonic acid diisopropyl ester 
• 146286-13-7 [2-Hydroxy-2-(4-isopropenyl-cyclohex-1-enyl)-ethyl]-phosphonic acid diisopropyl ester 
• 68305-45-3 trans-Di-isopropyl-1-propenylphosphonat 
• 4252-89-5 diphenyl(prop-1-en-1-yl)phosphine oxide 
• 993-13-5 methylphosphonic acid 
• 227747-71-9 bis(1-methylethyl) [(5Z,7E,22E)-(1S,3R)-1,3-bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-24-oxo-24a-homo-9,10-secochola-5,7,10⁽¹⁹⁾,22-tetraen-24a-yl]phosphonate 
• 72019-17-1 (+/-)-diisopropyl 2-hydroxy-2-phenylethylphosphonate 
• 800407-55-0 (2S,3S,4R)-diisopropyl 3-(N-benzylamino)-3-(2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)propylphosphonate 
• 146286-19-3 (E)-6-(Diisopropoxy-phosphoryl)-3-phenyl-hex-4-enoic acid ethyl ester 
• 146286-20-6 {2-[2-(Diisopropoxy-phosphoryl)-eth-(E)-ylidene]-5-isopropenyl-cyclohexyl}-acetic acid ethyl ester 
• 122768-66-5 1-(((diisopropyloxyphosphinyl)methyl)isopropyloxyphosphinyl)-2-phenylethane 

Relevant academic research and scientific papers

Structure and reactivity of mixed alkali metal alkoxide/aryloxide catalysts

The average solution aggregation state of the ester interchange catalyst 1, obtained by mixing 1 equiv of NaOt-Bu and 3 equiv of NaOC6H4-4-t-Bu, was determined to be 4.0 by vapor pressure osmometry (VPO) in THF. Low-temperature 1H NMR spectra of 1 indicated that the THF solution contained a mixture of tetrameric clusters. On the basis of symmetry arguments and the sensitivity of the different species to the alkoxide/aryloxide ratio, the compounds were determined to be mixed clusters with 0:4, 1:3, 2:2, and 3:1 mixtures of the NaOt-Bu and NaOC6H4-4-t-Bu components. On a per -Ot-Bu basis, each cluster has a similar absolute activity, though the aryloxide-rich catalysts are significantly longer-lived. Unlike 1, catalysts containing ortho-substituted aryloxides, 2, do not give a strictly statistical distribution of clusters, and the activities of these catalysts depend on steric and electronic factors, though the absolute rate differences are not large.

Solvent-Free Michaelis-Arbuzov Rearrangement under Flow Conditions

The first solvent- and catalyst-free procedure for the Michaelis-Arbuzov reaction under flow conditions was developed. A variety of alkylphosphonic esters could be obtained using this protocol starting from the corresponding trialkyl phosphites and even catalytic amounts of alkyl halides with very short reaction times (8.33-50 min) and excellent conversions. In general, this protocol works effectively when the alkyl halide is used in catalytic amounts as low as 5-10% only if it concerns the synthesis of homo alkylphosphonates. One equivalent and an excess of alkyl halides should be used in the reaction with alkyl phosphite if the alkyl group of the selected substrates differ. Thus, it provides a sustainable, fast alternative to the existing methods for the preparation of alkylphosphonates. The isolation of the reaction products is straightforward due to the lack of solvents and a high purity of the obtained products (conv ≥ 99%), and notably, in the catalytic procedures there are only traces of alkyl halides formed after the reaction is complete. The reactions conducted using a glass microreactor chip with an internal volume of 250 μL allow the production of 1.6-1.95 g of organophosphorus esters per hour.

Phase-transfer-catalyzed Michaelis-Becker synthesis of dialkyl methyl phosphonates

A liquid-liquid phase-transfer-catalyzed (PTC) Michaelis-Becker reaction was adopted in the preparation of dialkyl methyl phosphonate (R=Me, iPr; nBu, and iBu). This was performed by the reaction of an appropriate dialkyl hydrogen phosphonate with methyl iodide in the presence of benzyl triethyl ammonium chloride and sodium hydroxide as PTC and base, respectively. A liquid-liquid two-phase system (H2O/CH2Cl2) introduced a suitable situation for the preparation of dialkyl methyl phosphonates with bulky alkyl groups (R=iPr, nBu, and iBu), but with R=Me, the hydrolysis of dimethyl hydrogen phosphonate (reagent) reduced the yield to 22%. In this case, a solid-liquid PTC-free system was successfully applied and yield of over 80% was obtained. Copyright Taylor & Francis Group, LLC.

Stereocontrolled synthesis of planar chiral carba-paracyclophanes via modular assembly

Described herein is a flexible modular approach to planar chiral carba-paracyclophanes via the stepwise assembly of two distinct side arms and the aromatic core followed by ring-closing olefin metathesis. Planar chirality is induced by one chiral sulfinyl group by forming a hydrogen bond to the phenol in the aromatic unit.

Microwave-assisted ionic liquid-catalyzed selective monoesterification of alkylphosphonic acids—an experimental and a theoretical study

It is well-known that the P-acids including phosphonic acids resist undergoing direct es-terification. However, it was found that a series of alkylphoshonic acids could be involved in mo-noesterification with C2–C4 alcohols under microwave (MW) irradiation in the presence of [bmim][BF4] as an additive. The selectivity amounted to 80–98%, while the isolated yields fell in the range of 61–79%. The method developed is a green method for P-acid esterification. DFT calculations at the M062X/6–311+G (d,p) level of theory (performed considering the solvent effect of the corresponding alcohol) explored the three-step mechanism, and justified a higher enthalpy of activation (160.6–194.1 kJ·mol–1) that may be overcome only by MW irradiation. The major role of the [bmim][BF4] additive is to increase the absorption of MW energy. The specific chemical role of the [BF4] anion of the ionic liquid in an alternative mechanism was also raised by the computations.

PHOSPHONATE CONJUGATES AND USES THEREOF

Phosphonate conjugates, preferably, bisphosphonate conjugates; methods of inhibiting Ron receptor tyrosine kinase and methods of treatment of bone destruction due to cancer or other conditions utilizing the provided phosphonate conjugates.

Discovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer

Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as an attractive approach for the development of cancer immunotherapy. In this study, a series of phosphonamidate ester containing compounds were designed, synthesized and evaluated for their inhibitory activities against IDO1. Among them, compounds 16, 17, and 26 with good IDO1 inhibitory (HeLa IDO1 IC50 = 10–21 nM, hIDO1 IC50 = 78–121 nM) activities were selected for further investigation and showed good physicochemical properties. Furthermore, based on comparable PK profile and excellent IDO2/TDO inhibitory potency, representative compound 16 was selected for further bio-evaluation and characterized with good efficacy in suppressing lung metastasis (77% inhibition rate) of Lewis cells in vivo. Thus, compound 16 could be a potential and efficacious agent for further evaluation.

Synthesis of the Tripeptides Tyr-Thr-Lys Phosphorylated with Isopropyl Methyl- and (Deuteromethyl)phosphonochloridates as Reference Standards for the Analysis of Biomedical Samples

A procedure for the phosphorylation of the tripeptide Tyr-Thr-Lys with isopropyl methyl- or (deuteromethyl)phosphonochloridate is developed. The phosphorylated tripeptides are intended for use as reference standards in the analysis of blood samples of people suspected to have been exposed to acetylcholinesterase inhibitors. Conditions of hromatographic separation and purification of the synthesized compounds are determined and optimized, which ensures the preparation of high-purity phosphorylated tripeptides.

Facile Synthesis of Stereodefined α-Iodovinyl Sulfoxides, Versatile Platform to Trisubstituted Olefins

Stereodefined α-iodovinyl sulfoxides bearing a sulfinyl group and an iodo group were prepared by a one-pot iodination/Horner-Wadsworth-Emmons reaction protocol. This reaction can be applied to a wide range of aldehydes, and further application was demonstrated.

Polymer-supported sulfonated magnetic resin: An efficient reagent for esterification of O-alkyl alkylphosphonic-and carboxylic-acids

A mild and efficient synthetic method has been developed for the esterification of O-alkyl alkylphosphonic-and carboxylic-acids using polymer-supported sulfonated magnetic resins. Polymer-supported resins are recovered using an external magnet and reused several times.