反应详情

(10,11 -Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-((3R)-3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-methanone of Step B (0.500 g, 1.21 mmol), and N,N-diisopropylethyl amine (0.442 mL, 2.54 mmol) were dissolved in anhydrous dichloromethane (12.1 mL). Trichloroacetyl chloride (0.297 mL, 2.66 mmol) was then added dropwise and the reaction was stirred at room temperature for 3.5 hours, diluted with ethyl acetate and washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was filtered through a plug of silica gel eluting with 30% ethyl acetate in hexane, and the filtrate was concentrated to afford the crude bis-trichloroacetate as a brown foam. This material was dissolved in acetone (8.1 mL) and treated with 2.5 N sodium hydroxide (1.94 mL, 4.84 mmol). After stirring at room temperature for 2.5 hours, the reaction mixture was acidified with 1 N hydrochloric acid (50 mL) and extracted with diethyl ether. The combined organic extracts were extracted with 1 N sodium hydroxide and the basic extracts combined and acidified with 2 N hydrochloric acid. Upon acidification, a precipitate formed which was filtered and dried to afford 0.510 g of the title compound as a brown solid, [α]589=+17.84 (c=1.0, chloroform).

1. washwashed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine
2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. filtrationThe residue was filtered through a plug of silica gel eluting with 30% ethyl acetate in hexane
6. concentrationthe filtrate was concentrated
7. customto afford the crude bis-trichloroacetate as a brown foam
8. stirringAfter stirring at room temperature for 2.5 hours
9. extractionextracted with diethyl ether
10. extractionThe combined organic extracts were extracted with 1 N sodium hydroxide
11. customUpon acidification, a precipitate formed which
12. filtrationwas filtered
13. customdried