Large-scale preparation of (+)-p-menth-2-ene-1,8-diol, a key intermediate in the synthesis of δ-9-tetrahydrocannabinol

Organic Process Research and Development

Volumn 13, Issue 2, 2009, Pages 358-361

  Cabaj, John E ^a,b   Lukesh, Julie M ^a   Pariza, Richard J ^a   Zizelman, Paul M ^a  

^a Cedarburg Pharmaceuticals   (United States)

^b UNIVERSITY OF WISCONSIN GREEN BAY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 65949090760     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op8002272     Document Type: Article

References (20)

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2. For asymmetric syntheses see: Trost, B. M.; Dogra, K. Org. Lett. 2007, 9, 861.
3. Evans, D. A.; Barnes, D. M.; Johnson, J. S.; Lectka, T.; von Matt, P.; Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E. A.; Campos, K. R. J. Am. Chem. Soc. 1999, 121, 7582.
4. For a racemic synthesis starting from non-terpenoid starting materials see: Fahrenholtz, K. E.; Lurie, M.; Kierstead, R. W. J. Am. Chem. Soc. 1967, 89, 5934.
5. (a) Handrick, G. R.; Uliss, D. B.; Dalzell, H. C.; Razdan, R. K. Tetrahedron Lett. 1979, 20, 681.
6. (b) Stoss, P.; Merrath, P. Synlett 1991, 553.
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8. (d) Casner, M.; Resnick, T. M.; Silverberg, L. J. World Patent Application WO 02/096846, 2002.
9. (e) Silverberg, L. J. World Patent Application WO 02/096899 A1, 2002.
10. See: Cabaj, J. E.; Pariza, R. J.; Lukesh, J. World Patent Application WO 2005/100333, 2005 for coverage of this work and other methods to produce THC.
11. Prasad, R. S.; Dev, S. Tetrahedron 1976, 32, 1437.
12. Bledoe, J. O., Jr.; Derfer, J. M.; Johnson, W. E., Jr. U.S. Patent 3, 814, 733, 1974.
13. Acharya, S. P.; Brown, H. C. J. Am. Chem. Soc. 1967, 89, 1925.
14. The cost per mole of oxidant for peracetic acid is 34/mol, whereas the cost for MCPBA is 93/mol (2007-2008 Aldrich catalog pricing).
15. Bach, R. D.; Knight, J. W. Org. Synth. 1981, 60, 63.
16. Arias, L. A.; Adkins, S.; Nagel, C. J.; Bach, R. D. J. Org. Chem. 1983, 48, 888.
17. The main decomposition product formed from 1 upon continued exposure to acid is l-methyl-4-(1-methylvinyl) cyclohex-2-ene-1-ol 9.
18. f difference between 7/4 and 1 is approximately 0.6 using 1:1 EtOAc/heptanes as the eluent.
19. Other examples of this approach were kindly brought to our attention by a reviewer. Chen, C.-K.; Singh, A. K. Org. Process Res. Dev. 2001, 5, 508.
20. Chang, J. H.; Hyunik, S. Org. Process Res. Dev. 2008, 12, 291.