1034305-21-9

Basic information

• Product Name: D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-
• Synonyms: D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-;(1S)-1,5-Anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-D-glucitol 2,3,4,6-tetraacetate;(1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-D-glucitol
• CAS NO: 1034305-21-9
• Molecular Formula: C₂₉H₂₉FO₉S
• Molecular Weight: 572.5985632
• Mol File: 1034305-21-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 634.8±55.0 °C(Predicted)
• Appearance: /
• Density: 1.35±0.1 g/cm3(Predicted)
• CAS DataBase Reference: D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-(CAS DataBase Reference)
• NIST Chemistry Reference: D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-(1034305-21-9)
• EPA Substance Registry System: D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-(1034305-21-9)

Safety Data

• Hazardous Substances Data: 1034305-21-9(Hazardous Substances Data)

Usage

General Description

"D-Glucitol, 1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylMethyl)-4-fluorophenyl]-, 2,3,4,6-tetraacetate, (1S)-" is a complex organic chemical compound. It is contributing with its D-glucitol (a type of sugar alcohol) based structure that has been derivatized with a benzo[b]thien-2-ylMethyl group, a 4-fluorophenyl group, and four acetyl groups. The '(1S)-' at the end of its name indicates its spatial configuration is in the 'S' (sinister or left-handed) direction, referring to its stereochemistry. Despite the complexity of its structure and name, the actual properties, uses, and effects of this specific compound are not immediately apparent and require further investigation.

Synthetic route

methyl 2,3,4,6-tetra-O-acetyl-1-C-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-α-glucopyranoside (1034305-27-5) → (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9)

Conditions	Yield
With trifluorormethanesulfonic acid; tert-butyldimethylsilane In toluene; acetonitrile at -9.2 - 1℃;
With triethylsilane; boron trifluoride diethyl etherate In acetonitrile at -5 - 0℃; for 4h; Reagent/catalyst; Temperature;	21 g

C21H21FO6S + acetic anhydride (108-24-7) → (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9)

Conditions	Yield
With pyridine; dmap In dichloromethane at 25℃; for 2h; Temperature; Industrial scale;	0.58g

2-[(5-bromo-2-fluorophenyl)methyl]-1-benzothiophene (1034305-17-3) → (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: s-butylmagnesium chloride; n-butyllithium; lithium chloride / tetrahydrofuran; hexane / 3.17 h / -10 °C / Inert atmosphere; Industrial scale 1.2: 3 h / -10 °C / Industrial scale 2.1: pyridine; dmap / dichloromethane / 2 h / 25 °C / Industrial scale View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 1 h / -60 °C / Inert atmosphere 1.2: 5 h / -60 °C 2.1: sulfuric acid / 20 h / -15 - 10 °C 3.1: dmap; triethylamine / toluene / 5 h / 15 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / acetonitrile / 4 h / -5 - 0 °C View Scheme

(3R,4S,5R,6R)-3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one (32469-28-6, 55515-28-1, 55515-29-2, 32384-65-9) → (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: s-butylmagnesium chloride; n-butyllithium; lithium chloride / tetrahydrofuran; hexane / 3.17 h / -10 °C / Inert atmosphere; Industrial scale 1.2: 3 h / -10 °C / Industrial scale 2.1: pyridine; dmap / dichloromethane / 2 h / 25 °C / Industrial scale View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 1 h / -60 °C / Inert atmosphere 1.2: 5 h / -60 °C 2.1: sulfuric acid / 20 h / -15 - 10 °C 3.1: dmap; triethylamine / toluene / 5 h / 15 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / acetonitrile / 4 h / -5 - 0 °C View Scheme

C33H53FO6SSi4 → (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / 20 h / -15 - 10 °C 2: dmap; triethylamine / toluene / 5 h / 15 °C 3: triethylsilane; boron trifluoride diethyl etherate / acetonitrile / 4 h / -5 - 0 °C View Scheme

(1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9) → (2S,3R,4R,5S,6R)-2-(3-(benzo[b]thiophen-2-ylmethyl)-4-fluorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (761423-87-4) + (1R)-1,5-anhydro-1-{3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl}-D-glucitol

Conditions	Yield
With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 15℃; for 4h; Temperature; Reagent/catalyst; Concentration; Industrial scale;	A 99.5% B 99%

(1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol (1034305-21-9) → (2S,3R,4R,5S,6R)-2-(3-(benzo[b]thiophen-2-ylmethyl)-4-fluorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (761423-87-4)

Conditions	Yield
Stage #1: (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl]-D-sorbitol With methanol; water; sodium hydroxide at 25 - 49.1℃; Stage #2: With hydrogenchloride In methanol; water at 20.2 - 60℃;	97%
With water; potassium carbonate In toluene at 10℃;	80.1%

Upstream product

• 32469-28-6 (3R,4S,5R,6R)-3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one 
• 1034305-17-3 2-[(5-bromo-2-fluorophenyl)methyl]-1-benzothiophene 
• 108-24-7 acetic anhydride 
• 1034305-27-5 methyl 2,3,4,6-tetra-O-acetyl-1-C-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-α-glucopyranoside 

Downstream Products

• 761423-87-4 (2S,3R,4R,5S,6R)-2-(3-(benzo[b]thiophen-2-ylmethyl)-4-fluorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol 

Relevant articles and documents

Preparing methods of ipragliflozin intermediates

The invention discloses preparing methods of ipragliflozin intermediates. The methods includes preparing methods for 2-(3-benzo[B]thien-2-ylmethyl-4-fluorophenyl)-3,4,5-tris(trimethylsiloxy)-6-trimethylsiloxymethyl-tetrahydro-pyran-2-ol (a compound 3) and (1S)-2,3,4,6-tetraacetoxy-1,5-anhydro-1-[3-(1-benzothiophen-2-yl-methyl)-4-fluorophenyl]-D-glucitol (a compound 6). Under the premise of controlling the temperature of a reaction solution to be not higher than -60 DEG C, n-butyllithium should be added dropwise as soon as possible, and the higher the adding speed of the n-butyllithium is, theless F-ortho-position substituted side products of the compound 3 are, thus ensuring purity of the compound 3 and directly influencing the yield of the compound 6 finally prepared. Through scale-up, the methods are free of scale-up effects, and are suitable for industrial production.

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