反应详情

(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-(3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-methanone of Example 9 (0.590 g, 1.43 mmol), and N,N-diisopropylethyl amine (1.25 mL, 7.15 mmol) were dissolved in anhydrous dichloromethane (7.2 mL) followed by dropwise addition of trichloroacetyl chloride (0.638 mL, 5.72 mmol). The reaction was stirred at room temperature overnight, diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the residue filtered through a plug of silica gel eluting with 30% ethyl acetate in hexane. The filtrate was concentrated and the residue dried in vacuo to afford the crude bis-trichloroacetate as an orange oil which was redissolved in acetone (9.5 mL) and treated with 2.5 N aqueous sodium hydroxide (2.86 mL, 7.15 mmol). The reaction mixture was stirred at room temperature for 18 hours, acidified with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic phase was extracted with 1 N sodium hydroxide and the combined basic extracts acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 10% methanol in chloroform, to afford 0.320 g of the title compound as a brown solid which was used as such in the next step.

1. washwashed with water, 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 filtered through a plug of silica gel eluting with 30% ethyl acetate in hexane
6. concentrationThe filtrate was concentrated
7. customthe residue dried in vacuo
8. customto afford the crude bis-trichloroacetate as an orange oil which
9. stirringThe reaction mixture was stirred at room temperature for 18 hours
10. extractionextracted with ethyl acetate
11. extractionThe organic phase was extracted with 1 N sodium hydroxide
12. extractionextracted with ethyl acetate
13. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was purified by flash column chromatography on silica gel eluting with 10% methanol in chloroform