反应详情

To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(tert-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals.

1. customThe solvent was evaporated
2. dissolutionthe residue was dissolved in tetrahydrofuran (6 ml)
3. customat 0° C.
4. stirringthe mixture was stirred at room temperature for 16 hours
5. extractionthe mixture was extracted with ethyl acetate
6. washThe extract was washed with saturated sodium chloride solution
7. dry with materialdried with magnesium sulfate
8. customThe solvent was evaporated
9. customCrude amide (1.1 g) was obtained from fractions of hexane
10. stirringThe mixture was stirred for 1 hour
11. filtrationwas filtered
12. dissolutionwhich were dissolved in acetone
13. dry with materialThe mixture was dried with magnesium sulfate
14. customthe solvent was evaporated
15. customThe resulting powder was recrystallized from acetone-diisopropyl-ether