5-Phenoxy-1(3H)-isobenzofuranone

In a stirred three-necked flask equipped with 40 g of sodium hydroxide, Add 200 mL of water to dissolve and cool to 0-5 ° C. Then, 100 g of the intermediate N, methyl-4-phenoxy-phthalimide prepared in the previous step was fed in batches, About 1h cast, 0-5 insulation 1-2h. Thin layer chromatography to the disappearance of raw materials after adding 130g zinc powder and 200mL water, heated to 90 , Insulation reaction 5h, After the end of insulation to room temperature, The filter cake was washed with 50 ml * 2. The filtrate and hydrochloric acid adjusted PH = 1, the temperature to 80 , Insulation 1-2h, after the end of insulation to room temperature, With 30percent sodium hydroxide to adjust the pH to 5-7, filter, filter cake washed with water, After drying, add to 150mL methanol at room temperature for half an hour, filter, The filter cake was washed with methanol 30 mL * 2 and the product was removed by drying to give 75 g of product, 85percent yield and 99percent purity.In a stirred three-necked flask equipped with 40 g of sodium hydroxide, Add 200mL water dissolved, cooled to 0-5 , Then, 94 g of the intermediate 4-phenoxy-phthalimide prepared in the previous step was fed in batches and incubated at 0 to 5 ° C for 1 to 5 hours. Thin layer chromatography to the disappearance of raw materials by adding 130 g of zinc powder and 200 mL of water, Heat up to 90 , insulation reaction 5h, after the end of insulation to room temperature, filtration, filter cake with 50ml * 2 washing. The filtrate and hydrochloric acid adjusted PH = 1, the temperature to 80 , insulation 1-2h, After the end of the insulation to reduce, with 30percent of sodium hydroxide PH PH to 5-7, The filter cake was washed with water, dried and then added to 150 mL of methanol. The mixture was stirred at room temperature for half an hour. The filter cake was washed with methanol 30 mL * 2 and the product was taken out to obtain 74 g of product, yield 83percent and HPLC purity 98percent.A 1000 mL autoclave was charged with 60 g of 2-bromo-5-phenoxybenzyl alcohol (Compound 3), 300 g of toluene, 30 g of triethylamine, and 30 mg of palladium acetate.150 mg of 4, 5-bisdiphenylphosphine-9, 9-dimethylxanthene and 0.9 g of 8-hydroxyquinoline copper, cover the kettle lid, vacuum replacement three times; pass carbon monoxide gas to a pressure of 1.0- 1.5MPa, heat up to 140°C, The reaction was maintained until the starting 2-bromo-5-phenoxybenzyl alcohol (Compound 3) was < 3percent. The reaction is over, The material was cooled to room temperature, carbon dioxide was replaced with nitrogen and 200 g of water was added.The resulting triethylamine hydrobromide was dissolved by stirring. 10g of cellulose was added to the reaction material and stirred for 1 hour. The insoluble matter was removed by filtration; the filtrate was allowed to stand and stratified, and the aqueous layer was discarded.The organic layer was washed with 5percent hydrochloric acid until acidic. Organic layer decompression recovery of toluene, Add 200g of methanol to the residue and warm it up to 60-70°C to dissolve the solid.Then add 5g of activated carbon to decolorize for 30 minutes;The filtrate was slowly cooled to 0-5°C to crystallize. The solid obtained was filtered and dried at 60° C. under atmospheric pressure to give 5-phenoxyphenylhydrazine (Compound 1) as a product with a yield of 80percent and a purity of 99.53percent.Add phenol (20.4g, 0.22mol) and DMF 50mL to the reaction flask and start stirring.5-Bromoisobenzofuran-1(3H)-one (34.0 g, 0.16 mmol), acetylacetone (3.2 g, 0.03 mol), cuprous bromide (3.6 g, 0.03 mol), potassium carbonate (at room temperature) 30.8g, 0.22mol), three times of nitrogen replacement, heating to 90 ° C, stirring reaction overnight, adding 1000 mL of purified water to the reaction solution, suction filtration, the filter cake was dissolved in 800 mL of dichloromethane, and the organic phase was washed with 800 mL of 1N hydrochloric acid solution, with purified water. 1000 mL washing, drying the organic phase, and concentrating to dryness under reduced pressure to give a yellow solid.The title compound 2b (22.5 g, 63percent) was obtained.A mixture of 5-bromo-3H-isobenzofuran- 1 -one (75.9 g, 0.36 mol) (Sigma-Aldrich), phenol (67.1 g, 0.713 mol), CuCl (17.6 g, 0.178 mol), 2, 2, 6, 6-tetramethyl-heptane-3, 5-dione (TMHD, 7.33 mL) and cesium carbonate (232.3 g, 0.713 mol) in NMP (200 mL) was heated at 130 °C for 64 h. After cooled, reaction mixture was poured into ice/2M HCl mixture (1 L). The mixture was then refluxed for 1 h. After cooled, the solid was collected, rinsed with water and dried in vacuo to provide the title compound (72.22 g, 0.32 mol).

Molecular Weight:226.23
XLogP3:2.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:226.062994177
Monoisotopic Mass:226.062994177
Topological Polar Surface Area:35.5
Heavy Atom Count:17
Complexity:283
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes