Isoquinoline Alkaloids. 2. Preparation of d,l-Glaucine 1.5 Phosphate from d,l-Laudanosoline Hydrobromide

A high-yield, commercially viable synthesis of d,l-glaucine 1.5 phosphate (1) from d,l-laudanosoline hydrobromide (2) is described. Oxidation of 2 with ferric chloride in ethanol/ water buffered with sodium acetate gave d,l-1,2,9,10-tetrahydroxyaporphine hydrochloride (3) in 76−83% yield. This was c...

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Bibliographic Details
Published in:Organic process research & development 1997-07, Vol.1 (4), p.273-279
Main Authors: Goralski, Christian T, Hasha, Dennis L, Henton, Daniel R, Krauss, Richard C, Pfeiffer, Curtis D, Williams, Billy M
Format: Article
Language:English
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Summary:A high-yield, commercially viable synthesis of d,l-glaucine 1.5 phosphate (1) from d,l-laudanosoline hydrobromide (2) is described. Oxidation of 2 with ferric chloride in ethanol/ water buffered with sodium acetate gave d,l-1,2,9,10-tetrahydroxyaporphine hydrochloride (3) in 76−83% yield. This was converted to the free base, 4, which was methylated with phenyltrimethylammonium hydroxide (5) in 1,2-dichlorobenzene to give, after precipitation with 48% hydrobromic acid, crude d,l-glaucine hydrobromide (6) in 74% yield. The crude 6 was purified by recrystallization from 50/50 (v/v) ethanol/water to remove by-product 1-(2-(dimethylamino)ethyl)-3,4,6,7-tetramethoxyphenanthrene hydrobromide (7). The purified 6 was converted to 1 in 86−88% yield by formation of the free base followed by treatment with 85% phosphoric acid in 80% ethanol and subsequent crystal digestion for 6 h.
ISSN:1083-6160
1520-586X
DOI:10.1021/op970216u