7-Veratrylbutyric acid

The ethyl 7-veratrylbutyrate, b.p. 203-207°/20 mm., is obtained in 80% yield by esterification of 7-veratrylbutyric acid by the Fischer-Speier method. The 7-veratrylbutyric acid is prepared by the method of E. L. Martin from /3-(3,4-dimethoxy-benzoyl)-propionic acid. 

The synthesis of the homophthalic acid was a rather involved one, requiring as primary starting material /3-veratrylbutyric acid. It was necessary to block the 6-position with a bromine atom, ring-close to the corresponding 4-bromo-6,7-dimethoxy-3-methyl-l-indanone, and then treat the isonitroso derivative of this with p-toluenesulfonyl chloride in the presence of alkali. The resulting carboxy nitrile on hydrolysis and de-bromination with sodium amalgam afforded the desired acid. Similar syntheses are described in greater detail in the chapter on protopine and cryptopine. 

In a procedure for the synthesis of 6,7-dimethoxy-3,4-dihydro-2-naphthoic acid (IV) by the method of G. P. Crowley and R. Robinson, ethyl y-veratrylbutyrate (I) is formylated with ethyl formate by dropwise addition of a solution of 1 and ethyl formate in ether to a suspension of sodium ethoxide in ether at —10°. After acidification, the formyl derivative II is collected by ether extraction and cyclized to III with a mixture of 90% phosphoric acid and concentrated sulfuric acid at 0-10°. Saponification gives the acid IV, m.p. 193°. 

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