反应详情

To 2-(7-chloro-3-(2-chlorobenzyl)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-1-yl)ethyl acetate (0.62 g, 1.47 mmol) suspended in tetrahydrofuran (10 mL) was added 2M aqueous sodium hydroxide (2.2 mL, 4.4 mmol). Methanol (2 mL) was added, which caused the solution to become homogeneous. The solution was stirred at ambient temperature for 2 hours, then acidified with 1M hydrochloric acid, partitioned between ethyl acetate and brine, separated, dried with sodium sulfate, filtered and concentrated in vacuo. The resulting solid was dissolved in N,N-dimethylformamide (10 mL), and imidazole (0.14 g, 2 mmol) was added followed by tert-butyldimethylsilyl chloride (0.24 g, 1.6 mmol). This mixture was stirred at ambient temperature overnight, then diluted with ethyl acetate, washed with 10% citric acid, water, and brine, dried with sodium sulfate, filtered and concentrated in the presence of silica gel. The product was purified by column chromatography eluting with a gradient of 0-50% ethyl acetate in hexanes to yield 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-7-chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione.

1. custompartitioned between ethyl acetate and brine
2. customseparated
3. dry with materialdried with sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe resulting solid was dissolved in N,N-dimethylformamide (10 mL)
7. stirringThis mixture was stirred at ambient temperature overnight
8. washwashed with 10% citric acid, water, and brine
9. dry with materialdried with sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in the presence of silica gel
12. customThe product was purified by column chromatography
13. washeluting with a gradient of 0-50% ethyl acetate in hexanes