Synthesis of indoles with functionalized substituents

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the 

Fischer indole cyclizations incorporating functionalized substituents 

4 1 -(4-Chlorobenzyl)-2-(2-ethoxy-carbonyl-2-methylpropyl)-3-raethyl EtOH, cat. H2SO4 68 [5] 

5 3-[2-. cetaraido-2,2-bis-(ethoxy- carbonyl)ethylJ-7-chloro 5% HjSO 99 [6] 

10 3-(t-Butylthio)-2-[2-(methoxy-carbonyl)- 2-mcthy Ipropyl]- 5-(2-propenyloxy) HOAc, NaOAc 31 [11] 

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