1373321-04-0

Basic information

• Product Name: (2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
• CAS NO: 1373321-04-0
• Molecular Weight: 408.879
• Mol File: 1373321-04-0.mol

Chemical Properties

• Boiling Point: 609.0±55.0 °C(Predicted)
• Density: 1.349±0.06 g/cm3(Predicted)
• CAS DataBase Reference: (2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol(1373321-04-0)
• EPA Substance Registry System: (2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol(1373321-04-0)

Safety Data

• Hazardous Substances Data: 1373321-04-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol is used as a pharmaceutical compound for its potential therapeutic properties. The specific application reason is not provided in the materials, but the compound's structure suggests it may have biological activity or serve as a precursor to other bioactive molecules.
Used in Chemical Synthesis:
In the field of chemical synthesis, (2R,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol can be used as a building block or intermediate for the synthesis of more complex molecules. Its unique stereochemistry and functional groups make it a valuable component in the development of new drugs, materials, or other specialty chemicals.

Upstream product

• 864070-19-9 [4-(5-bromo-2-chloro-benzyl)-phenoxy]-tert-butyl-dimethyl-silane 
• 1204220-63-2 (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 
• 864070-37-1 (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol 
• 80-40-0 ethyl ester of p-toluenesulfonic acid 
• 1103738-26-6 (2-chloro-5-iodo-phenyl)-(4-ethoxyphenyl)methanone 
• 12167-34-9 (2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-(4-methoxyphenoxy)tetrahydro-2H-pyran-3,4,5-triol 
• 4132-28-9 (3R,4R,5R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-ol 
• 461432-26-8 dapagliflozin 
• 1335-57-5 3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-one 
• 461432-22-4 (5-bromo-2-chlorophenyl)(4-ethyloxyphenyl)methanone 
• 21900-52-7 5-bromo-2-chloro-benzoyl chloride 
• 21739-92-4 5-bromo-2-chlorobenzoic acid 
• 960494-15-9 C₃₃H₅₇ClO₇Si₄ 
• 32469-28-6 (3R,4S,5R,6R)-3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one 

Downstream Products

• 1181680-68-1 (2R,4R,5S,6S)-4,5-bis(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)dihydro-2H-pyran-3(4H)-one 
• 1443356-49-7 (1S)-1,5-Anhydro-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-deoxy-6-(hydroxyamino)-d-glucitol 
• 1443356-45-3 (1S)-1,5-Anhydro-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-deoxy-6-[2-(furan-2-ylcarbonyl)-hydrazinyl]-d-glucitol 

Relevant articles and documents

A Concise and Efficient Synthesis of Dapagliflozin

A concise and efficient synthesis of the SGLT-2 inhibitor dapagliflozin (1) has been developed. This route involves ethyl C-aryl glycoside 9 as the key intermediate, which is easily crystallized and purified as the crystalline n-propanol solvate with high purity (>98.5%). The tetra-O-unprotected compound 9 could be directly reduced to crude dapagliflozin with high diastereoselectivity. The final pure API product 1 was isolated and purified with high purity (>99.7%). The process has been implemented on a multikilogram scale.

Fluorophore-dapagliflozin dyad for detecting diabetic liver/kidney damages via fluorescent imaging and treating diabetes via inhibiting sglt2

Type II diabetes is a prevalent disease; if left untreated, it could cause serious complications including liver and kidney damages. Hence, early diagnosis for these damages and effective treatment of diabetes are of high importance. Herein, a fluorophore-dapagliflozin dyad (DX-B-DA) has been developed as a theranostic system that can be triggered by intrahepatic/ intrarenal reactive oxygen species (ROS) to concomitantly release a near-infrared (NIR) fluorescent dye (DX) and a SGLT2 inhibitor dapagliflozin (DA). In this dyad (DX-B-DA), the NIR fluorophore (DX) and the drug DA were covalently linked through a boronate ester bond which serves as the fluorescence quencher as well as the ROS-responsive moiety that can be cleaved by pathological levels of ROS in diabetics. The in vitro experiments indicate that, in the absence of hydrogen peroxide, the dyad is weakly emissive and keeps its drug moiety in an inactive state, while upon responding to hydrogen peroxide, the dyad simultaneously releases the NIR dye and the drug DA, suggesting that it can serve as an activatable probe for detecting and imaging diabetic liver/ kidney damages as well as a prodrug for diabetes treatment upon being triggered by ROS. The dyad was then injected in mouse model of type II diabetes, and it is found that the dyad can not only offer visualized diagnosis for diabetes-induced liver/kidney damages but also exhibit high efficacy in treating type II diabetes and consequently ameliorating diabetic liver/kidney damages.

Facile and green synthesis of dapagliflozin

A facile and green synthetic route was developed for the preparation of dapagliflozin (1), a selective sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes. Key reaction steps include a direct Friedel–Crafts acylation and a synthesis of diaryl ketal moiety in one-pot manner without waste water generation. Furthermore, the reduction of the diaryl ketone and C-phenylglucoside were achieved in one-pot manner to generate dapagliflozin (1) more efficiently. The synthetic route featured the usage of commercial available and easily handling reagents with shorter reaction steps and less waste disposal.

Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols

Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectivel

Preparation method of dapagliflozin

The invention relates to a preparation method of dapagliflozin. The preparation method comprises the following steps: reacting a compound 1 serving as a raw material with butyl lithium in an organic solvent at a low temperature, adding a compound 2, carrying out a series of reactions to prepare a compound 3 with higher purity, reacting the compound 3 with silane and boron trifluoride acetic acid or boron trifluoride diethyl etherate to prepare a compound 4. A tedious reaction process is avoided, and the utilization rate of raw materials and the purity of products are improved. The method for preparing dapagliflozin has the advantages of simple operation, high product conversion rate (up to 99%), few impurities, and high product purity, and is suitable for industrial production.

Method for synthesizing diabetes medicine by D - gluconic acid - δ δ-lactone

The invention discloses a method for synthesizing a diabetes drug by D - gluconic acid - δ δ-lactone. To the technical field of drug synthesis, D - glucose acid - δ δ-lactone is used as a raw material, and then subjected to catalytic hydrogenation and bromination reaction through three-silyl protecting reaction, then condensed with 5 - bromo -2 - chloro -4’ - ethoxy diphenyl methane, and finally, trimethyl silicon-based protection is removed. To the method for synthesizing the diabetes medicine by D - gluconic acid - δ δ-lactone, D - gluconic acid - δ δ-lactone is adopted as the starting raw material, the reaction process is simple, the intermediate is easy to purify, and the raw materials used in the reaction are easily obtained. The reaction process is more mild than the prior art. The yield of the final product can reach 95.89% or above, and the purity can reach 99.5% or more.

Facile Approach to C-Glucosides by Using a Protecting-Group-Free Hiyama Cross-Coupling Reaction: High-Yielding Dapagliflozin Synthesis

Access to unprotected (hetero)aryl pseudo-C-glucosides via a mild Pd-catalysed Hiyama cross-coupling reaction of protecting-group-free 1-diisopropylsilyl-d-glucal with various (hetero)aryl halides has been developed. In addition, selected unprotected pseudo-C-glucosides were stereoselectively converted into the corresponding α- and β-C-glucosides, as well as 2-deoxy-β-C-glucosides. This methodology was applied to the efficient and high-yielding synthesis of dapagliflozin, a medicament used to treat type 2 diabetes mellitus. Finally, the versatility of our methodology was proved by the synthesis of other analogues of dapagliflozin.

Preparation method of dapagliflozin

The invention discloses a preparation method of dapagliflozin. The preparation method comprises the following steps: (1) reacting a compound solution as shown in a formula II and an n-butyllithium solution in a first microreactor in a microchannel reaction device; (2) reacting effluent of the first microreactor with a compound as shown in a formula III in a second microreactor in the microchannel reaction device to obtain a compound as shown in a formula IV; (3) carrying out reduction reaction on the compound shown in the formula IV in a third microreactor in the microchannel reaction device to obtain a compound shown in a formula V; and (4) deprotecting the compound as shown in the formula V to obtain dapagliflozin as shown in the formula I. According to the method disclosed by the invention, benzyl-protected glucolactone is adopted as a starting raw material, so that generation and multiple derivatization of isomer impurities and ring-opening impurities are avoided, the stereoselectivity is relatively high, and post-treatment steps and waste generation are reduced; and meanwhile, the yield is high, the purity is high, the synthesis steps are few, the operation is simple and convenient, and the safety is high.

PREPARATION OF HIGHLY PURE AMORPHOUS DAPAGLIFLOZIN

A novel and improved process for the preparation of amorphous dapagliflozin is disclosed. The present invention further provides pharmaceutical compositions containing amorphous dapagliflozin, optionally in a combination with one or more other active substances and methods for making the same.

Syntheses of SGLT2 inhibitors by Ni- And Pd-catalyzed fukuyama coupling reactions

Nickel- and palladium-catalyzed Fukuyama coupling reactions of a D-gluconolactone-derived thioester with arylzinc reagents at ambient temperature provided the corresponding multifunctional aryl ketones in high yield. Ligand screening for the nickel-catalyzed Fukuyama coupling reactions indicated that 1,2- bis(dicyclohexylphosphino)ethane (dCype) served as a superior supporting ligand to improve the product yield. In addition, Pd/C was a practical alternative that enabled ligand-free Fukuyama coupling reactions and was efficiently applied to the key C-C bond-forming step to prepare canagliflozin and dapagliflozin, which are diabetic SGLT2 inhibitors of current interest.