Ethyl 7-methoxyindole-3-acetate

A new synthesis of ethyl 7-methoxyindole-3-acetate was accomplished by reductive cyclization of the o-nitrobenzyl cyanide 22a. The indole was then elaboarated to the tetracycle 22d by an intramolecular Pummerer reaction. <95JHC947> ch2co2c2h5... 

The next three procedures provide useful synthetic intermediates. A stereospecific synthesis of ETHYL (Z)-3-BROMO-2-PROPENOATE affords an alternative vinyl bromide partner for the coupling chemistry in the preceding procedure. A very simple but elegant illustration of the flash vacuum pyrolysis technique is used to prepare BENZOCYCLOBUTENONE from o-toluoyl chloride. Another member of the functionalized indole family of synthetic intermediates is presented in a four-step procedure for 5-METHOXYINDOLE-2-ACETIC ACID METHYL ESTER. 

Catalytic hydrogenation of the molecule 137, which is available by exposure of l-methoxy-4-nitro-2-(trifluoro-methyl)benzene to 4-chlorophenoxyacetonitrile in the presence of potassium /-butoxide, provided a practical approach to the indole 138 (Equation 38) <1998JME1598>. A related strategy has also been used in preparation of pyrroloquinolines <2002H(57)129> and ethyl (7-methoxyindol-3-yl)acetate <1995JHC947>. 

A soln. of K-nitrosodisulfonate and NaHCOg added simultaneously with ethyl acetate to a stirred aq. soln. of methyl 3-hydroxy-4-methoxyphenylalaninate, and the product isolated after 0.5 hr. from the 2-phase system methyl 5-hydroxy-6-methoxyindole-2-carboxylate. Y 68%. M. E. Wilcox et ah, Helv. 4-8, 252 (1965). 

N-[2-( 1 -Methoxyindol-3-yl)ethyl]-1 -methoxyindole-3-acetamide (43a), its AT-methyl analog (43b), and Ar-[2-(l-methoxyindol-3-yl)ethyl]indole-3-acet-amide (51) are prepared by the following route (Scheme 8) [23]. 

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