反应详情

Trifluoroacetic acid (4 mL) was added to crude carbamate 10.6 (1.030 g). After 20 min at rt most of the volatiles were removed in vacuo and 1 M HCl (10 mL) was added, whereupon an oil separated. This was washed with DCM (3×3 mL). The aqueous portion was basified to pH>12 with 5 M NaOH, extracted with DCM (3×4 mL), dried (MgSO4), filtered and concentrated to an oil (10 mg). The initial DCM washing was dried (MgSO4), filtered and concentrated to a pale yellow oil (1.26 g), whose 1H NMR was consistent with being the piperidinium trifluoroacetate. This material, plus the initial collected free base (10 mg) was dissolved in ether (30 mL) and washed with 5 M NaOH (10 mL), 1 M NaOH (2×10 mfL), water (10 mL) and saturated NaCl (2×10 mL), then dried (MgSO4) and filtered. HCl—saturated ether (35 mL) was added and the turbid solution was extracted with 1 M HCl (3×10 mL). The acidic portion was basified with 5 M NaOH, extracted with DCM (3×8 mL) and the organic portion dried (MgSO4), filtered and concentrated to a pale yellow oil (457 mg; 62% from 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester). LC (method B) tR=8.2 min; 1H NMR (200 MHz, CDCl3) δ 7.37 (dd, J=1.6, 8.0 Hz, 1H), 7.19 (ddd, J=1.5, 7.3, 8.6 Hz, 1H), 7.0-6.8 (m, 2H), 4.42 (tt, J=3.9, 3.9 Hz, 1H), 3.18 (ddd, J=4.0, 6.3, 12.0 Hz, 2H), 2.73 (ddd, J=3.7, 8.6, 12.3 Hz, 2H), 2.00 (m, 2H), 1.77 (m, 2H); ESIMS (free base) 212.0/213.9 (100/37) [MH+].

1. customAfter 20 min at rt most of the volatiles were removed in vacuo and 1 M HCl (10 mL)
2. additionwas added, whereupon an oil
3. customseparated
4. washThis was washed with DCM (3×3 mL)
5. extractionextracted with DCM (3×4 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated to an oil (10 mg)
9. dry with materialThe initial DCM washing was dried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated to a pale yellow oil (1.26 g), whose 1H NMR
12. customThis material, plus the initial collected free base (10 mg)
13. dissolutionwas dissolved in ether (30 mL)
14. washwashed with 5 M NaOH (10 mL), 1 M NaOH (2×10 mfL), water (10 mL) and saturated NaCl (2×10 mL)
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. additionHCl—saturated ether (35 mL) was added
18. extractionthe turbid solution was extracted with 1 M HCl (3×10 mL)
19. extractionextracted with DCM (3×8 mL)
20. dry with materialthe organic portion dried (MgSO4)
21. filtrationfiltered
22. concentrationconcentrated to a pale yellow oil (457 mg; 62% from 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester)