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 phosph ate (1) from d,l-laudanosoline hydrobromide (2) is described. Oxidatio n of 2 with ferric chloride in ethanol/water buffered with sodium acet ate 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 g ive, after precipitation with 48% hydrobromic acid, crude d,l-glaucine hydrobromide (6) in 74% yield. The crude 6 was purified by recrystall ization from 50/50 (v/v) ethanol/water to remove by-product ethylamino )-ethyl-3,4,6,7-tetramethoxyphenanthrene hydrobromide (7). The purifie d 6 was converted to 1 in 86-88% yield by formation of the free base f ollowed by treatment with 85% phosphoric acid in 80% ethanol and subse quent crystal digestion for 6 h.