Phenylhydrazine hydrochloride → 2-(4-Methoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[b]indole

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Reaction Steps

A mixture of 3-(4-methoxyphenyl)-1-cyclopentanone (15.22 g) and phenyl hydrazine hydrochloride (11.57 g) in glacial acetic acid (112 ml) under nitrogen was stirred magnetically and slowly heated to 90° with a heating mantle. A white precipitate, which formed at approximately 60°, dissolved to give a red solution as the temperature rose exothermically to 110°. As soon as the solid had dissolved, the heating mantle was removed and the temperature allowed to return to 90° for 1 hr. The cooled solution was poured into 400 ml of water. After refrigeration, the supernatant liquid was filtered. The filter pad and residual material were dissolved in chloroform and the solution was washed with saturated sodium bicarbonate solution. The dried (MgSO4) solution was evaporated to a syrup which was subjected to an oil pump vacuum; wt. 19.4 g (92%). This material was chromatographed on a column (60×7.6 cm) of silica gel prepacked in chloroform. Elution with chloroform afforded a mixture of the titled product and 1,2,3,4-tetrahydro-1-(4-methoxyphenyl)-cyclopent[b]indole in a ratio of 3:2 as determined by a reverse phase HPLC system (see Example 2). After solvent removal the residual syrup was coevaporated with acetonitrile to give 11.90 g (56.5%) of a red syrup which began to crystallize on standing. Crystallization from acetonitrile-water (seeding) gave crude product; wt. 5.25 g (24.9%), mp=107°-109°. Recrystallization from acetonitrile-water gave the titled product as pale yellow crystals, wt. 4.39 g, mp=109°-111°.

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