反应详情

温度

90 °C

1-(4′-Fluorophenyl)-1,3-dihydroisobenzofuran-5-carbaldehyde (17.00 g) was dissolved in toluene (200 ml) and hydroxylamine hydrochloride (5.5 g) and triethylamine (8.0 g) were added. The mixture was stirred at 80-100° C. for 2 hr. The obtained triethylamine hydrochloride was filtered and the solvent was evaporated. Thereto was added acetic anhydride (36.5 g) and the mixture was stirred at 125-130° C. for 5 hr. The reaction mixture was poured into 10% aqueous sodium hydroxide solution (300 ml) and extracted twice with toluene (200 ml). The toluene layer was washed successively with 5% aqueous sodium hydroxide solution, water and saturated brine and dried over magnesium sulfate. Silica gel (5 g) was added and the mixture was thoroughly stirred and filtered. The solvent was evaporated to give crude 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (14.2 g). This was recrystallized from a mixed solvent of ethanol/hexane to give 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (9.52 g, 59.8%).

1. filtrationThe obtained triethylamine hydrochloride was filtered
2. customthe solvent was evaporated
3. additionThereto was added acetic anhydride (36.5 g)
4. stirringthe mixture was stirred at 125-130° C. for 5 hr
5. additionThe reaction mixture was poured into 10% aqueous sodium hydroxide solution (300 ml)
6. extractionextracted twice with toluene (200 ml)
7. washThe toluene layer was washed successively with 5% aqueous sodium hydroxide solution, water and saturated brine
8. dry with materialdried over magnesium sulfate
9. additionSilica gel (5 g) was added
10. stirringthe mixture was thoroughly stirred
11. filtrationfiltered
12. customThe solvent was evaporated
13. customto give crude 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (14.2 g)
14. customThis was recrystallized from a mixed solvent of ethanol/hexane