With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.82104-74-3,1-Oxo-1,3-dihydroisobenzofuran-5-carbonitrile,as a common compound, the synthetic route is as follows.
82104-74-3, 1048g of a 10percent solution of 4-fluorophenylmagnesium bromide in tetrahydrofuran are added to a suspension of 60.Og of 5-cyanophthalide in 390ml of 1 ,2-dimethoxyethane at -100C within three hours. After stirring for 30 minutes at -100C, the cold reaction mixture is poured into 1L of aqueous NH4CI (18Og in 1000ml of water, 200C) in about 5 minutes. The layers are separated and the aqueous layer is extracted with 300ml of tetrahydrofuran. The organic layers are combined and volatiles are removed under reduced pressure at 45¡ãC. The residue is dissolved in a mixture of 100OmL of CH2CI2 and 200ml of water containing 2.5g of sodium carbonate (pH of 9). The layers are separated and the organic phase is dried with 4Og of sodium carbonate. The dry CH2CI2 solution is treated with 6g of charcoal, stirred for 10 minutes and the charcoal is removed by filtration. The filter cake is washed with 5OmL of CH2CI2. Filtrate and washing liquid are combined and the solvent is removed under reduced pressure. 30OmL of diisopropylether are added to the residue. After stirring for 1 hour at 22¡ãC the crystal suspension is cooled to 0¡ãC and stirred for another two hours, then cooled to -100C and stirred for 14 hours. The product is isolated by filtration and washed with 4OmL of chilled diisopropylether, 8OmL of a 1 :1 mixture of diisopropylether/cyclohexane and 8OmL of cyclohexane. After drying for 3 hours at 50¡ãC in vacuo 83.0 g (86.2 percent of theory, purity (HPLC): 99.8 areapercent) white, crystalline powder of the title compound are obtained (mp. 85¡ãC).1H-NMR (CDCI3, 300MHz): delta 3.01 (t, J = 6.30, 0.8 H, OH), 3.66 (s, 0.2 H, OH), 4.66 (d, J = 6.11 Hz, 1.6 H, CH2-O), 5.33 (m, CH2-O, 0.4 H, lactol-isomer), 7.03 – 7.93 (m, 7 H, ArH)
The synthetic route of 82104-74-3 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; SANDOZ AG; WO2007/82771; (2007); A1;,
Benzofuran – Wikipedia
Benzofuran | C8H6O – PubChem