反应详情

To a suspension of sodium hydride (0.32 g of a 60% dispersion in mineral oil) in N,N-dimethylformamide (30 ml) was added gradually (3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1 H-1,4-benzodiazepin-2-one (2.87 g) under nitrogen atmosphere at cooling in an ice-bath. The mixture was stirred under the same condition for 0.5 hour and at ambient temperature for 1 hour. The mixture was cooled in an ice-bath and a sodium iodide (1.18 g) was added thereto in one portion. To the mixture was added dropwise a solution of 3-chloromethylpyridine (1.00 g) and stirred for 0.5 hour at the same temperature. The mixture was stirred overnight at ambient temperature. To the resultant was added acetic acid (1.5 g) under cooling in an ice-bath. The resultant mixture was poured into water (100 ml) and extracted with ethyl acetate (100 ml). The aqueous layer was adjusted to pH 7.0-8.0 with sodium carbonate and extracted with ethyl acetate (2×50 ml). The combined organic layer was washed with brine and dried over sodium sulfate, filtered and concentrated in vacuo to give a crude compound. The crude compound was purified by flash chromatography on silica gel [eluent (CHCl3 :ethyl acetate =1:1)] to afford (3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1-(pyridin-3-yl)-methyl-1H -1,4-benzodiazepin-2-one as a colorless crystalline solid (0.67 g).

1. temperatureat cooling in an ice-bath
2. temperatureThe mixture was cooled in an ice-bath
3. stirringstirred for 0.5 hour at the same temperature
4. stirringThe mixture was stirred overnight at ambient temperature
5. temperatureunder cooling in an ice-bath
6. extractionextracted with ethyl acetate (100 ml)
7. extractionextracted with ethyl acetate (2×50 ml)
8. washThe combined organic layer was washed with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give a crude compound
13. customThe crude compound was purified by flash chromatography on silica gel [eluent (CHCl3 :ethyl acetate =1:1)]