1298086-18-6

Basic information

• Product Name: (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyltriacetate
• Synonyms: (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyltriacetate;EOS-60361;5-C-[(Acetyloxy)methyl]-1,6-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-beta-L-idopyranose 2,3,4-triacetate
• CAS NO: 1298086-18-6
• Molecular Formula: C₃₀H₃₃ClO₁₁
• Molecular Weight: 605.02942
• Mol File: 1298086-18-6.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 633.3±55.0 °C(Predicted)
• Appearance: /
• Density: 1.35±0.1 g/cm3(Predicted)
• CAS DataBase Reference: (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyltriacetate(CAS DataBase Reference)
• NIST Chemistry Reference: (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyltriacetate(1298086-18-6)
• EPA Substance Registry System: (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyltriacetate(1298086-18-6)

Safety Data

• Hazardous Substances Data: 1298086-18-6(Hazardous Substances Data)

Usage

Uses

(1R,2S,3S,4R,5S)-1-(Acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl Triacetate is an antidiabetic agent and an Ertugliflozin (1210344-57-2) intermediate.

Synthetic route

Ertugliflozin (1210344-57-2) + acetic anhydride (108-24-7) → (1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl triacetate (1298086-18-6)

Conditions	Yield
With pyridine In toluene at 5 - 20℃; for 24.25h; Inert atmosphere;	89%
With pyridine In toluene at 5 - 20℃; for 24.25h;	5.4%

(1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl triacetate (1298086-18-6) → Ertugliflozin (1210344-57-2)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 0.25h;
With sodium methylate In methanol at 20℃; for 3.25h; Inert atmosphere;

(1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl triacetate (1298086-18-6) → ((1R,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)-phenyl)-2,3,4-trihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)methyl acetate (1298086-20-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium methylate / methanol / 0.25 h / 20 °C 2: pyridine / toluene / 8.28 h / -10 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium methylate / methanol / 3.25 h / 20 °C / Inert atmosphere 2: pyridine / toluene / 19.1 h / -10 - 20 °C / Inert atmosphere View Scheme

(1R,2S,3S,4R,5S)-1-(acetoxymethyl)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl triacetate (1298086-18-6) → (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol (1:1) compound with (S)-5-oxopyrrolidine-2-carboxylic acid (1210344-83-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium methylate / methanol / 0.25 h / 20 °C 2.1: methanol; water; isopropyl alcohol / 40 - 60 °C / 30 Torr 2.2: 40 - 80 °C View Scheme
Multi-step reaction with 2 steps 1: sodium methylate / methanol / 3.25 h / 20 °C / Inert atmosphere 2: water; isopropyl alcohol / 10 h / 40 - 80 °C / Inert atmosphere View Scheme

Upstream product

• 1210344-57-2 Ertugliflozin 
• 108-24-7 acetic anhydride 

Downstream Products

• 1210344-57-2 Ertugliflozin 
• 1298086-20-0 ((1R,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)-phenyl)-2,3,4-trihydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl)methyl acetate 
• 1210344-83-4 (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol (1:1) compound with (S)-5-oxopyrrolidine-2-carboxylic acid 

Relevant articles and documents

AN EFFICIENT PROCESS FOR THE PREPARATION OF ERTUGLIFLOZIN L-PYROGLUTAMIC ACID AND INTERMEDIATES THEREOF

The present invention relates to an efficient process for the preparation of Ertugliflozin L-pyroglutamic acid of formula (I) and intermediate thereof, in environment friendly conditions. The present invention further relates to a process for the preparation of substantially pure intermediate of formula (IV).

Commercial route research and development for SGLT2 inhibitor candidate ertugliflozin

A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations over a 12-step sequence. The dioxabicyclo[ 3.2.1]octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-D-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with L-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.