Dapagliflozin ((2S)-1,2-propanediol, hydrate)

Base Information

• Chemical Name: Dapagliflozin ((2S)-1,2-propanediol, hydrate)
• CAS No.: 960404-48-2
• Molecular Formula: C₃H₈O₂*C₂₁H₂₅ClO₆*H₂O
• Molecular Weight: 502.99
• Mol file: 960404-48-2.mol

Synonyms:Dapagliflozin ((2S)-1,2-propanediol, hydrate);Dapagliflozin propylene glycolate hydrate;Forxiga;Dapagliflozin (S)-Propylene Glycol Hydrate;Dag column net a water glycol;Dapagliflozin propanediol hydrate;Dapagliflozin,(2S)-1,2-propanediol, hydrate (1:1:1)

Chemical Property of Dapagliflozin ((2S)-1,2-propanediol, hydrate)

Chemical Property:

• PSA: 149.07000
• LogP: 1.13960
• Storage Temp.: -20°C Freezer
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

98% ^*data from raw suppliers

DapagliflozinPropanediolHydrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Dapagliflozin Propanediol Hydrate is an SGLT2 inhibitor, which can be used for the treatment of diabetes.
• Clinical Use: The most likely process-scale synthesis has been described in a literature publication and patent, and this is summarized in the scheme below. The synthesis began with global silylation glucolactone 63 to form tetrasiloxide 64. In parallel, commercial 5-bromo-2-chlorobenzoyl acid (65) was converted to the corresponding acid chloride with oxalyl chloride. Subsequently, this acid chloride was subjected to Friedel-Crafts acylation with ethyl phenyl ether (“phenetole”) in the presence of aluminum trichloride at low temperature to give benzophenone 66 in 91% yield. Next, the carbonyl functionality within 66 was removed upon treatment with triethylsilane and boron trifluoride-etherate, producing 5-bromo-2-chloro- 4'-ethoxydiphenylmethane 67 in 75% yield as the aglycon partner. Aryl bromide 67 was subjected to lithium halogen exchange conditions and subsequent exposure to lactone 64, which gave a mixture of lactols which were then immediately subjected to methanesulfonic acid to provide glucol 68 in 85% yield. The anomeric methoxy group of 68 was reduced with triethylsilane and boron trifluoride-etherate followed by peracetylation to deliver α-C-glycoside tetra-acetate 69 in 55% (two steps) after recrystalliaztion in ethanol. Hydrolysis of polyacetate 69 with lithium hydroxide gave dapagliflozin in quantitative yield, and upon treatment with propanediol in water, dapagliflozin propanediol hydrate (X) was produced.

Technology Process of Dapagliflozin ((2S)-1,2-propanediol, hydrate)

There total 2 articles about Dapagliflozin ((2S)-1,2-propanediol, hydrate) which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 60.0%

(S)-1,2-Propanediol (4254-15-3,63625-56-9) + (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetraol → dapagliflozin (S) propylene glycol hydrate (960404-48-2)

Guidance literature:

(3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetraol; With triethylsilane; boron trifluoride diethyl etherate; In acetonitrile; at 0 - 25 ℃; Inert atmosphere;

(S)-1,2-Propanediol; With water; In tert-butyl methyl ether;

Reference yield: 4.0%

dapagliflozin (461432-26-8,1373321-04-0) + (S)-1,2-Propanediol (4254-15-3,63625-56-9) → dapagliflozin (S) propylene glycol hydrate (960404-48-2)

Guidance literature:

With water; In tert-butyl methyl ether; cyclohexane; for 1h; Product distribution / selectivity;

upstream raw materials:

dapagliflozin

(S)-1,2-Propanediol

Refernces

• 1、 -. "CRYSTAL STRUCTURES OF SGLT2 INHIBITORS AND PROCESSES FOR PREPARING SAME". Page/Page column 21-22. . Retrieved 2008/06/13.