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

Abstract

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.