反应详情

To an ice/water bath cooled crude 4,5-dibromo-2-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-1-(4-fluoro-benzyl)-1H-pyrrole-3-carboxylic acid ethyl ester (29.49 g) in toluene (100 mL) was added a 25% (weight) concentration of potassium tert-pentoxide in toluene (67.04 mL) during a course of ˜5 min; after that, the reaction was stirred for 1 h in the cold bath and then poured to a stirring mixture of ice/water and ammonium chloride, organic phase was separated and washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated to give the cyclized intermediate. The intermediate was then dissolved in 50 mL toluene and 50 mL TFA and stirred at room temperature for 1 h, then concentrated, the residue was partitioned between toluene and water; the organic phase was washed once with saturated sodium hydrogen carbonate, saturated sodium chloride solution respectively, then dried over anhydrous sodium sulfate, filtered, and air bubbled through the filtrate for a period of overnight. The precipitates were collected as the first crop of the title product (8.161 g). The filtrate was concentrated and purified with column directly to give the second crop of the title product (4.98 g). The title compound, ESI MS (m/z): 489 (M+H)+.

1. customwas separated
2. washwashed with water and saturated sodium chloride solution
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the cyclized intermediate
7. concentrationconcentrated
8. customthe residue was partitioned between toluene and water
9. washthe organic phase was washed once with saturated sodium hydrogen carbonate, saturated sodium chloride solution respectively
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationfiltered
12. customair bubbled through the filtrate for a period of overnight
13. customThe precipitates were collected as the first crop of the title product (8.161 g)
14. concentrationThe filtrate was concentrated
15. custompurified with column directly