反应详情

To a stirred solution of 1-[3-(ethyloxy)-4-nitrophenyl]piperazine (Example 143, step A) (0.53 g, 2.1 mmol) and 1-BOC-4-piperidone (2.1 g, 10.6 mmol) in DCE (21 mL) was added HOAc (0.25 g, 4.2 mmol) followed by addition of sodium triacetoxyborohydride (2.2 g, 10.6 mmol). The reaction was stirred under N2 at rt for 3 h. The reaction was quenched with aqueous (saturated) NaHCO3 and extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum. The residue was dissolved and stirred in a 20% solution of TFA/DCM (50 mL) for approximately 2 h at rt. The mixture was concentrated under vacuum. The residue was dissolved in DCM and neutralized with aqueous (saturated) NaHCO3. The aqueous layer was extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum to give the title compound of step A (560 mg, 1.68 mmol, 79%) as a yellow solid. MS (ESI): 335 [M+H]+.

1. customThe reaction was quenched with aqueous (saturated) NaHCO3
2. extractionextracted with DCM (3×)
3. dry with materialThe combined organic layers were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated under vacuum
6. customThe residue was purified by silica gel chromatography
7. concentrationThe desired fractions were concentrated under vacuum
8. dissolutionThe residue was dissolved
9. stirringstirred in a 20% solution of TFA/DCM (50 mL) for approximately 2 h at rt
10. concentrationThe mixture was concentrated under vacuum
11. dissolutionThe residue was dissolved in DCM and neutralized with aqueous (saturated) NaHCO3
12. extractionThe aqueous layer was extracted with DCM (3×)
13. dry with materialThe combined organic layers were dried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated under vacuum
16. customThe residue was purified by silica gel chromatography
17. concentrationThe desired fractions were concentrated under vacuum