32384-65-9

Basic information

• Product Name: (3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one
• Synonyms: (3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one;(3R,4S,5R,6R)-3,4,5-Tris[(trimethylsilyl)oxy]-6-[[(trimethylsilyl)oxy]methyl]tetrahydropyran-2-one;2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone;D-2,3,4,6-Tetrakis-O-(trimethylsilyl)-gluconic acid delta-lactone;D-Gluconic acid, 2,3,4,6-tetrakis-O-(triMethylsilyl)-, δ-lactone;D-Gluconic acid, 2,3,4,6-tetrakis-O-(triMethylsilyl)-, d-lactone;2,3,4,6-Tetrakis-O-triMethylsilyl-D-gluconolactoe;2,3,4,6-tetrakis-O-trimethylsilyl-D-glucono1,5 lactone
• CAS NO: 32384-65-9
• Molecular Formula: C₁₈H₄₂O₆Si₄
• Molecular Weight: 466.86448
• EINECS: 1592732-453-0
• Mol File: 32384-65-9.mol
• Article Data: 92

Chemical Properties

• Boiling Point: 417℃
• Flash Point: 171℃
• Appearance: /
• Density: 0.97
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Sparingly), Ethyl Acetate (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one(32384-65-9)
• EPA Substance Registry System: (3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one(32384-65-9)

Safety Data

• Hazardous Substances Data: 32384-65-9(Hazardous Substances Data)

Usage

Description

It is usually used as the intermediate and raw material in the chemistry synthesis and pharmaceutical industry. Especially, this chemical has been widely used in the design and synthesis of sodium-glucose transporter inhibitors.1 For example, this substance can be employed as raw material in the preparation of (1s)-1,5-anhydro-1-c-[4-chloro-3-[(4-ethoxylphenyl)methyl]phenyl]-D-glucitol, which is commonly known as Dapagliflozin that act as the sodium dependent glucose transporters for treating type 2 diabetes.2 Moreover, it can also function as the intermediate for synthesizing empagliflozin, which is a novel and selective sodium glucose co-transporter-2 inhibitor.3 In addition, canagliflozin, another sodium glucose co-transporter-2 inhibitor, can be obtained by utilizing this substance as the intermediate.4

Uses

2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone is an antidiabetic agent and an intermediate of Dapagliflozin (D185370). 2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone acts as a reagent in the synthesis of trans-cyclohexane-bearing C-glucose as sodium glucose co-transporter 2 inhibitors.

Reference

Guo, C.; Hu, M.; DeOrazio, R. J.; Usyatinsky, A.; Fitzpatrick, K.; Zhang, Z. J.; Maeng, J. H.; Kitchen, D. B.; Tom, S.; Luche, M.; Khmelnitsky, Y.; Mhyre, A. J.; Guzzo, P. R.; Liu, S., The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties. Bioorg. Med. Chem. 2014, 22, 3414-3422. S Thirumalai Rajan; Eswaraiah, S., Process for the preparation of (1S)-1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxylphenyl)methyl]phenyl]-D-glucitol and its solvate thereof. US Patent 2015, WO 2015/132803 A2. Hrapchak, M.; Latli, B.; Wang, X. J.; Lee, H.; Campbell, S.; Song, J. J.; Senanayake, C. H., Synthesis of empagliflozin, a novel and selective sodium-glucose co-transporter-2 inhibitor, labeled with carbon-14 and carbon-13. J. Label. Compd. Radiopharm. 2014, 57, 687-694. Nomura, S.; Sakamaki, S.; Hongu, M.; Kawanishi, E.; Koga, Y.; Sakamoto, T.; Yamamoto, Y.; Ueta, K.; Kimata, H.; Nakayama, K.; Tsuda-Tsukimoto, M., Discovery of Canagliflozin, a Novel C-Glucoside with Thiophene Ring, as Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus. J. Med. Chem. 2010, 53, 6355-6360.

Chemical Properties

Pale yellow oil

Upstream product

• 90-80-2 D-Glucono-1,5-lactone 
• 75-77-4 chloro-trimethyl-silane 
• 999-97-3 1,1,1,3,3,3-hexamethyl-disilazane 
• 18156-74-6 1-(Trimethylsilyl)imidazole 
• 15892-28-1 (3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-one 
• 1335-57-5 3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-one 

Downstream Products

• 461432-24-6 (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 
• 1030825-21-8 methyl 1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methyl-phenyl)-D-glucopyranoside 
• 1050200-97-9 1-bromo-3-(4-ethylbenzyl)-5-(1-methoxy-D-glucopyranos-1-yl)-2-methyl-benzene 
• 960494-15-9 C₃₃H₅₇ClO₇Si₄ 
• 912917-83-0 (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 
• 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 
• 1204219-46-4 (3R,4S,5S,6R)-2-(4-chloro-3-((4-(ethoxy-d5)phenyl)methyl-d2)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 
• 1204222-07-0 (2S,3R,4S,5S,6R)-2-(4-chloro-3-((3,5-difluoro-4-(methoxy-d3)phenyl)methyl-d2)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 
• 1204222-75-2 (3R,4S,5S,6R)-2-(4-chloro-3-((4-(cyclopropyl-1-d)phenyl)methyl-d2)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 

Relevant articles and documents

SYNTHETIC ROUTES TO HIGHER-CARBON SUGARS. REACTION OF LACTONES WITH 2-LITHIO-1,3-DITHIANE

The per(trimethylsilyl) ether of D-glucono-1,5-lactone reacted with 2-lithio-1,3-dithiane to give, after removal of protecting groups, a 62 percent yield of 1-C-(1,3-dithian-2-yl)-α-D-glucopyranose (3) as a single tautomer; this product is formally a derivative of a 7-carbon, 1,2-dicarbonyl sugar.The crystalline 2,3,4,6-tetraacetate (4) of 3 was readily obtained, again as a single tautomer, and forcing conditions of acetylation led to the acyclic, enol hexaacetate in admixture with the cyclic pentaacetate (6) of 3.Desulfurization of the tetraacetate 4 with Raney nickel gave 1-deoxy-D-gluco-heptulose as its α-pyranose 3,4,5,7-tetraacetate, whereas similar desulfurization of the pentaacetate 6 was accompanied by removal of the tertiary acetoxyl group, providing stereospecific access to the C-β-D-glucosyl compound 2,6-anhydro-1-deoxy-D-glycero-D-gulo-heptitol as its 3,4,5,7-tetraacetate.To explore the effects of chain substituents on the tautomeric behavior of the lacton-derived adducts, the simple lactones 5-pentanolide, 4-butanolide, and 4-pentanolide were made to react with 2-lithio-1,3-dithiane, and the tautomeric compositions of the products wre examined before and after acetylation.This work establishes preparative access to 1,2-dicarbonyl sugars, higher ketoses, and C-glycosyl compounds from readily available lactone precursors.

Preparation method and application of 2, 3, 4, 6-tetra-O-trimethylsilyl-D-glucolactone

The invention relates to the technical field of medicine, in particular to a preparation method and application of 2, 3, 4, 6-tetra-O-trimethylsilyl-D-gluconolactone. According to the preparation method, D-gluconolactone and hexamethyldisilazane react in an ionic liquid, cations in the ionic liquid are alkyl imidazolium ions, and anions in the ionic liquid are hexafluorophosphate radicals, tetrafluoroborate radicals, tetrachloroaluminate radicals or chloride ions. The ionic liquid is stable during high-temperature distillation, the solvent after reaction can be recycled, the preparation methodhas few reaction steps, atom economy is high, and operation conditions are easy to control. The preparation method can be used for preparing canagliflozin.

Synthesis method and application of 1-methyl glucose

The invention discloses a synthesis method and application of 1-methyl glucose. The synthesis method comprises the following steps: dissolving gluconic acid delta-lactone in THF, adding N-methylmorpholine and TMSCl, reacting to obtain TMS-protected gluconic acid delta-lactone, dissolving the TMS-protected gluconic acid delta lactone in anhydrous THF, treating with methyl lithium or methyl magnesium bromide, reacting to obtain TMS-protected 1-methyl glucose, dissolving the TMS-protected 1-methyl glucose in acetonitrile-water, and removing TMS protection by adding H strong cation exchangeresin to obtain 1-methyl glucose. The effect of applying 1-methyl glucose to cigarette perfuming is mainly to improve the aroma quality and aroma quantity, reduce irritation and purify the aftertaste.

Telescoped lithiation, C-arylation and methoxylation in flow-batch hybrid toward the synthesis of canagliflozin

We report a highly efficient three-step flow-batch hybrid procedure for the synthesis of a key canagliflozin intermediate. The telescoped process provides exquisite control over an exothermic and mixing sensitive lithiation and subsequent C-arylation within a microstructured flow reactor. Methoxylation reagents are then added in flow, before reaching completion in a batch vessel. The flow process afforded the target intermediate in 76% yield, with a throughput of 26.8 g/h.