反应详情

A homogeneous yellow solution of tert-butyl 4-(1-methyl-1H-imidazole-5-carbonyl)piperidine-1-carboxylate (10.1 g, 34.4 mmol, Intermediate 1: step b) in DCM (172 mL) was treated with TFA (26.4 mL, 344 mmol) and stirred at room temperature for 2.5 hours. The reaction was concentrated from toluene (2×100 mL), and the resulting clear light amber residue was taken up in DCM (344 mL) and TEA (23.9 mL, 172 mmol). Acetic anhydride (3.91 mL, 41.3 mmol) was added dropwise and the reaction stirred at room temperature for 1 hour. The reaction was concentrated under high vacuum and the residue was purified by FCC using 95:5 DCM/MeOH with 2% TEA as eluent. The combined fractions were concentrated, dissolved in DCM (200 mL), and washed with water (2×200 mL) to remove TEA. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was triturated with MTBE (75 mL) at reflux for 15 minutes and then allowed to cool to room temperature. The mixture was filtered and the off-white filter cake was washed with MTBE (2×3 mL) to provide, after air drying at 100° C., the title compound as an off-white fine powder.

1. concentrationThe reaction was concentrated from toluene (2×100 mL)
2. stirringthe reaction stirred at room temperature for 1 hour
3. concentrationThe reaction was concentrated under high vacuum
4. customthe residue was purified by FCC
5. concentrationThe combined fractions were concentrated
6. dissolutiondissolved in DCM (200 mL)
7. washwashed with water (2×200 mL)
8. customto remove TEA
9. dry with materialThe organic layer was dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was triturated with MTBE (75 mL)
13. temperatureat reflux for 15 minutes
14. temperatureto cool to room temperature
15. filtrationThe mixture was filtered
16. washthe off-white filter cake was washed with MTBE (2×3 mL)
17. customto provide
18. customafter air drying at 100° C.