反应详情

tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (358 mg, 0.751 mmol) was treated with 25% TFA in dichloroethane (2 ml, 6.49 mmol) at room temperature for 1 h. Solvent was evaporated in vacuo and the residue was diluted with dichloromethane and washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude intermediate was dissolved in dichloromethane (10 mL). Triethylamine (0.209 ml, 1.501 mmol) and BOC anhydride (0.261 ml, 1.126 mmol) were added subsequently. The reaction mixture was stirred at room temperature for 1 h and the reaction was complete. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate. The aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10-30% ethyl acetate/hexanes) to give tert-butyl 5-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (266 mg) as a colorless oil.

1. customSolvent was evaporated in vacuo
2. additionthe residue was diluted with dichloromethane
3. washwashed with water and brine
4. dry with materialThe organic layer was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionthe crude intermediate was dissolved in dichloromethane (10 mL)
8. washwashed with saturated sodium bicarbonate
9. extractionThe aqueous layer was extracted with dichloromethane two more times
10. dry with materialThe combined organic layers were dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customthe crude product was purified by flash chromatography on silica gel using
14. washan automated ISCO system (40 g column, eluting with 10-30% ethyl acetate/hexanes)