5-Phenoxyisobenzofuran-1(3H)-one Chemical Properties

Boiling point:

422.5±45.0 °C(Predicted)

Density 

1.280

storage temp. 

2-8°C

Appearance

Light yellow to yellow Solid

InChI

InChI=1S/C14H10O3/c15-14-13-7-6-12(8-10(13)9-16-14)17-11-4-2-1-3-5-11/h1-8H,9H2

InChIKey

BTQCNYDOVASZJD-UHFFFAOYSA-N

SMILES

C1(=O)C2=C(C=C(OC3=CC=CC=C3)C=C2)CO1

5-Phenoxyisobenzofuran-1(3H)-one Usage And Synthesis

Description

5-Phenoxy-l(3H)-isobenzofuranone, with a phenoxy-substituted benzo five-membered ring lactone structure, is a useful intermediate in preparing the derivatives of isoquinoline. The most common method of preparing 5-Phenoxyisobenzofuran-1(3H)-one was utilized, the copper-catalyzed coupling reaction of 5-bromophthalide and phenol in the presence of a base[1].

Synthesis

The general procedure for the synthesis of 5-phenoxyisobenzofuran-1-(3H)-one from the compound (CAS: 63197-24-0) was as follows: 40 g of sodium hydroxide and 200 mL of water were added to a three-necked flask equipped with a stirrer, and after stirring until complete dissolution, the solution was cooled to 0-5 °C. Subsequently, 100 g of the intermediate N-methyl-4-phenoxyphthalimide was added in batches, and the dosing process was completed in about 1 hour. After the addition was completed, the reaction temperature was maintained at 0-5 °C and the reaction was continued for 1-2 hours. The progress of the reaction was monitored by thin layer chromatography (TLC), and after the feedstock completely disappeared, 130 g of zinc powder and 200 mL of water were added to the reaction system. The reaction mixture was heated to 90°C and the reaction was maintained at this temperature for 5 hours. After the reaction was completed, it was cooled to room temperature, the solid was collected by filtration and washed twice with 50 mL of water. The filtrates were combined and the pH was adjusted to 1 with hydrochloric acid and then kept at 80 °C for 1-2 hours. At the end of the reaction, cooled to room temperature, adjusted the pH to 5-7 with 30% sodium hydroxide solution, filtered to collect the solid and washed with water. The resulting solid was treated with 150 mL of methanol for half an hour at room temperature, filtered, washed twice with 30 mL of methanol, and dried to give 75 g of the target product 5-phenoxyisobenzofuran-1-(3H)-one in 85% yield and 99% purity.

References

[1] Xi-An Li . “Synthesis of 5-phenoxyisobenzofuran-1(3H)-one as a key intermedate of the drug roxadustat.” Tetrahedron Letters 61 32 (2020): Article 152181.

5-Phenoxyisobenzofuran-1(3H)-one(57830-14-5)Related Product Information

• 4-Aminophthalimide
• Roxadustat
• 5-Aminophthalide
• INDEX NAME NOT YET ASSIGNED
• methyl 2-(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxamido)acetate
• FG-4592 interMediate
• methyl2-(chloromethyl)-4-phenoxybenzoate
• Roxadustat Impurity
• 2-{[(methoxycarbonylmethyl)(toluene-4-sulfonyl)amino]methyl}-4-phenoxybenzoic acid methyl ester
• methyl 1-chloro-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate