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