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J. J. Org. Chem. 2003, 68, 9847.
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4879.
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2103.
N-oxide salt following treatment with a variety of acids
was found to have a marked effect on the amount of the
desired N-nor product formed.
The use of the tetrasodium meso-tetra(4-sulfonatophe-
nyl)porphine for the removal of iron as an alternative
to basic EDTA significantly improved the yields of
desired N-nor products. The TPPS procedure has dem-
onstrated tolerance to acetyl, benzoyl and naphthoylate
esters and hydroxyl groups. This modification has
potential applications in large, scale processes, as the
water, soluble porphyrin synthesis is straightforward
and inexpensive, and has the added benefit of being
recyclable through demetallation procedures, thus
reducing costs and enhancing efficiency of the
N-demethylation process.
12. Reynolds, W. L.; Schufman, J.; Chan, F.; Brasted, R. C.
Int. J. Chem. Kinet. 1977, 9, 777.
13. General method for TPPS procedure: Codeine methyl
ether (0.20 g, 0.64 mmol) was dissolved in methanol
(30 mL) and magnesium bis(monoperoxyphthalate)
hexahydrate (80%, 0.38 g, 0.77 mmol) was added. The
reaction mixture was stirred at rt for 45 min and then
filtered (Celite pad). The Celite pad was washed with
additional methanol and the filtrate was evaporated in
vacuo to give CME–N-oxide as a phthalate salt. The
crude N-oxide was redissolved in methanol (30 mL),
FeSO4Æ7H2O (0.289 g, 0.96 mmol) was added and the
reaction mixture was stirred for 6 h at rt. The methanol
was evaporated and the resultant orange solid was
dissolved in an aqueous solution of tetrasodium meso-
tetra(4-sulfonatophenyl)porphine (1.14 g, 1.11 mmol in
25 mL) and extracted with CHCl3 (4· 50 mL). The
organic extract was dried (MgSO4) and evaporated to
Acknowledgments
Financial support from the Centre for Free Radical
Chemistry and Biotechnology and an Australian Post-
graduate Award to S.T. are gratefully acknowledged.
The authors also thank GlaxoSmithKline for donation
of opiate starting materials.
Supplementary data
Supplementary data associated with this article can be
afford
a mixture of norcodeine methyl ether and
codeine methyl ether (0.1987 g). Column chromatogra-
phy using CHCl3/MeOH/28% NH4OH (89:10:1) as an
eluent afforded pure norcodeine methyl ether in 78%
yield.
References and notes
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14. Gathergood, N.; Scammells, P. J.; Fallon, G. D. Acta
Crystallogr. 2003, C59, 485.
15. Gathergood, N.; Scammells, P. J.; Fallon, G. D. Acta
Crystallogr. 2003, E59, 1918.