Phenylhydrazine → 2-methyl-3-propyl-1H-indole

Phenylhydrazine (162.2 g) was placed in a reaction flask fitted with a mechanical stirrer, reflux condenser with attached drying tube, internal thermometer, and addition funnel. Acetic acid (900 ml) was added, resulting in an orange solution. To this mixture was then added 2-hexanone (170 g) over 5 min, and the resulting mixture was heated to reflux with stirring for three hours. After cooling, the acetic acid solvent was removed by rotary evaporation, and the residue was poured into water (4.5 liters). This mixture was extracted three times with ethyl ether (1 liter each) and the combined organic extracts were washed twice with 1N HCl (1 liter each), once with water (1.5 liters), once with saturated sodium bicabonate solution (1 liter) and then once with brine (1 liter). The organic layer was then dried (MgSO4) and evaporated to afford an oil which was purified by two successive vacuum distillations. The title compound (72.1 g) was obtained as an oil distilling between 91.5° and 95° at a pressure of 0.0067 Pascals (0.05 mTorr). An additional portion of the title compound was obtained by chromatography of the stillpot residue over flash silica gel (500 g), eluting with dichloromethane. Evaporation of the appropriate fractions afforded more material which was combined with the distillate above to provide a total of 159.1 grams (61% yield) of the title compound, which was used immediately in step (c).

1. customfitted with a mechanical stirrer
2. temperaturereflux condenser
3. customwith attached drying tube
4. additioninternal thermometer, and addition funnel
5. additionAcetic acid (900 ml) was added
6. customresulting in an orange solution
7. temperaturethe resulting mixture was heated
8. temperatureto reflux
9. temperatureAfter cooling
10. customthe acetic acid solvent was removed by rotary evaporation
11. additionthe residue was poured into water (4.5 liters)
12. extractionThis mixture was extracted three times with ethyl ether (1 liter each)
13. washthe combined organic extracts were washed twice with 1N HCl (1 liter each), once with water (1.5 liters), once with saturated sodium bicabonate solution (1 liter)
14. dry with materialThe organic layer was then dried (MgSO4)
15. customevaporated
16. customto afford an oil which
17. distillationwas purified by two successive vacuum distillations

ORD record

ord-7867f7cefba54ee69ab72f8a2e4c676a

Source dataset

uspto-grants-1989_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04886800