(S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran Chemical Properties

Boiling point:

476.0±45.0 °C(Predicted)

Density 

1.578±0.06 g/cm3 (20 ºC 760 Torr)

storage temp. 

2-8°C(protect from light)

solubility 

DMSO, Methanol (Slightly, Sonicated)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C17H16ClIO2/c18-17-6-3-14(19)10-13(17)9-12-1-4-15(5-2-12)21-16-7-8-20-11-16/h1-6,10,16H,7-9,11H2/t16-/m0/s1

InChIKey

YLUHNGIWRCCQMQ-INIZCTEOSA-N

SMILES

O1CC[C@H](OC2=CC=C(CC3=CC(I)=CC=C3Cl)C=C2)C1

CAS DataBase Reference

915095-94-2

(S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran Usage And Synthesis

Physical Form

Solid

Uses

(3S)-3-[4-[(2-Chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran(915095-94-2) can be used as reactant/reagent in preparation of C-?aryl D-?glurofuranoside compounds useful as reference compounds in the quality control of gliflozin type medicine.

Description

(S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran is a pharmaceutical intermediate compound that is used in the preparation of empagliflozin. Empagliflozin is an inhibitor of sodium-glucose co-transporter protein-2 (SGLT2), which is used in the treatment of type 2 diabetes.

Uses

(S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran (compound 2d), a halogenated Phenstatin analog, is a microtubule destabilizing agent. (S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran shows anticancer activities[1].

Preparation

0.5 mol of (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone and 0.6 mol of aluminum chloride were added to 2 mol of methanol at a temperature of 20° C, and then 0.6 mol of triethylsilane was added to the mixed solution. The mixture was stirred at 25° C for 1 h.The conversion is determined by HPLC analysis. After the reaction is complete, it is extracted and distilled under reduced pressure.Finally, (3S)-3-[4-[(2-Chloro-5-iodophenyl)methyl]phenoxy]tetrahydro-furan (also known as (S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran) was obtained through purification.

Synthesis

(2-Chloro-5-iodophenyl)[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methanone (50 g, 116.5 mmol) was added to a 500 mL three-necked flask equipped with a thermometer, a reflux condenser, and a drying tube with THF (350 mL) and stirred at room temperature. Subsequently, NaBH4 (22.0 g, 582.5 mmol) and AlCl3 (39 g, 291.5 mmol) were added in batches, and vigorous bubbling was maintained during the reaction. After the addition was completed, the reaction mixture was heated and refluxed for 5 h. The progress of the reaction was monitored by TLC, and the reaction was stopped after confirming the complete conversion of the raw materials. After the reaction system was cooled to room temperature, it was slowly poured into a mixture consisting of 200 mL of ice water and 75 mL of 2M HCl with vigorous stirring for 30 min. After standing and layering, the aqueous phase was extracted with ethyl acetate (100 mL x 3). The organic phases were combined and washed sequentially with sodium bicarbonate solution to neutral, saturated sodium chloride solution (200 mL), dried and concentrated to give a light yellow solid crude product. The crude product was dissolved in a mixed solvent of 50 mL of water and 10 mL of ethanol and crystallized to give the white solid product (S)-3-(4-(2-chloro-5-iodophenyl)phenoxy)tetrahydrofuran (26.6 g) in 90% yield.

References

[1] Hu, S., et al. Design, synthesis and anticancer activities of halogenated Phenstatin analogs as microtubule destabilizing agent. Med Chem Res 28, 465–472 (2019).

(S)-3-(4-(2-Chloro-5-iodobenzyl)phenoxy)tetrahydrofuran(915095-94-2)Related Product Information

• (S)-(5-broMo-2-chlorophenyl)(4-(tetrahydrofuran-3-yloxy)phenyl)Methanone
• (3S,4R)-4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine
• Thiazole
• Copper(II) chloride dihydrate
• Tetrahydrofuran
• Dimethyl fumarate
• 1-Propanol
• Brexpiprazole Intermediate 1
• (R)-3-(p-toluenesulfonyl) oxytetrahydrofuran
• Empagliflozin
• (S)-(+)-3-Hydroxytetrahydrofuran
• 4-(5-broMo-2-chlorobenzyl)phenol
• (3S)-3-[4-[(5-Bromo-2-chlorophenyl)methyl]phenoxy]tetrahydrofuran
• Benzo[b]thiophene, 2-[(5-broMo-2-fluorophenyl)Methyl]-
• (2-Chloro-5-iodophenyl)[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methanone
• (2S,3R,4S,5S,6R)-2-(3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)-4-chlorophenyl)-tetrahydro-6-(hydroxyMethyl)-2-Methoxy-2H-pyran-3,4,5-triol
• 2,3,4,6-Tetra-O-benzyl-a-D-glucopyranosylbromide
• (2-Chloro-5-iodophenyl)(4-fluorophenyl)methanone