A practical preparation of (R)- and (S)-N-Boc-2-methylpiperidines

Tetrahedron Asymmetry

Volumn 8, Issue 8, 1997, Pages 1275-1278

  Doller, Darío ^a   Davies, Robert ^a   Chackalamannil, Samuel ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PIPERIDINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; REACTION ANALYSIS;

EID: 0031000573     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(97)00123-7     Document Type: Article

References (23)

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7. Munchhof, M. J.; Meyers, A. I. J. Org. Chem. 1995, 60, 7084. For related enantioselective syntheses of 2-alkylpiperidine derivatives see: (a) Jones, R. C. F.; Turner, I.; Howard, K. J. Tetrahedron Lett. 1993, 34, 6329.
8. Munchhof, M. J.; Meyers, A. I. J. Org. Chem. 1995, 60, 7084. For related enantioselective syntheses of 2-alkylpiperidine derivatives see: (a) Jones, R. C. F.; Turner, I.; Howard, K. J. Tetrahedron Lett. 1993, 34, 6329.
9. (b) Streith, J.; Boiron, A.; Paillaud, J.-L.; Rodriguez-Perez, E.-M.; Strehler, C.; Taschamber, T.; Zehnder, M. Helv. Chim. Acta 1995, 78, 61.
10. Marckwald, W. Ber. 1896, 29, 43. Also see: (a) Leithe, W. Monatsh. Chem. 1928, 50, 40.
11. Marckwald, W. Ber. 1896, 29, 43. Also see: (a) Leithe, W. Monatsh. Chem. 1928, 50, 40.
12. (b) Craig, J. C.; Roy, S. K. Tetrahedron 1965, 21, 401.
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15. (S)-2-Methylpiperidine is reported to have specific rotation varying from +3.91 to +36.4. Ref. 6, 7a-d.
16. Chackalamannil, S.; Davies, R. J.; Asberom, T.; Doller, D.; Leone, D. J. Am. Chem. Soc. 1996, 118, 9312. Also see: (a) Hart, D. J.; Wu, W.-L.; Kozikowski, A. P. J. Am. Chem. Soc. 1995, 117, 9369.
17. Chackalamannil, S.; Davies, R. J.; Asberom, T.; Doller, D.; Leone, D. J. Am. Chem. Soc. 1996, 118, 9312. Also see: (a) Hart, D. J.; Wu, W.-L.; Kozikowski, A. P. J. Am. Chem. Soc. 1995, 117, 9369.
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19. 3. However, upon addition of (R)-O-acetylmandelic acid, a homogeneous solution was obtained.
20. The absolute value of chemical shifts, given here for comparison, varied somewhat depending on concentration.
21. After a total of three recrystallizations, the ee of (S)-2-methyl-L-tartrate was about 92%.
22. 1 H NMR experiments were conducted on the crude product without further purification.
23. 1H NMR experiment was repeated in each case by addition of about 15 molar percent of racemic 2-methylpiperidine to the sample. As expected, this gave rise to an additional methyl doublet corresponding to the opposite enantiomer.