反应详情

To a −75° C. solution of 4-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1-carboxylic acid tert-butyl ester 2 (500 mg, 1.25 mmol) in THF (25 mL) was slowly added t-BuLi (1.47 mL, 2.5 mmol). The reaction mixture was stirred for 30 minutes at which time 2-fluoro-benzenesulfonyl fluoride 2a (222 mg, 1.5 mmol) was added. The reaction was stirred for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm over 45 min. The reaction mixture was quenched with a saturated solution of ammonium chloride (55 mL). The mixture was then extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL). The organic layer was dried (MgSO4), filtered, and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexane:ethyl acetate (17:3) to afford 300 mg (43%) of 4-(4-tert-butoxycarbonyl-piperazin-1-yl)-2-(2-fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester (1-3).

1. customTo a −75° C.
2. additionwas added
3. customwas removed
4. temperatureto warm over 45 min
5. customThe reaction mixture was quenched with a saturated solution of ammonium chloride (55 mL)
6. extractionThe mixture was then extracted with ethyl acetate (3×20 mL)
7. washThe combined ethyl acetate layers were washed with brine (25 mL)
8. dry with materialThe organic layer was dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a yellow oil
12. customThe oil was chromatographed over silica eluting with hexane:ethyl acetate (17:3)