Hydrochloric Acid → 1-(4-methylphenyl)-3-(propan-2-yl)-1H-pyrazol-5-amine

Participants

Reaction Steps

To a mixture of acetonitrile (0.50 mL, 9.57 mmol) in THF (30 ml) at RT was added potassium 2-methylbutan-2-olate (1.7M solution in 2-methyl-butan-2-ol, 16.9 mL, 28.7 mmol). On completion of the addition ethyl isobutyrate (5.12 mL, 38.3 mmol) was added dropwise and the mixture was maintained at RT for 16 hr. The reaction mixture was concentrated in vacuo to ca 20 mL, was diluted with ethanol (20 mL) and p-tolylhydrazine hydrochloride (1.52 g, 9.57 mmol) was added. The resulting mixture was acidified to pH1 by the addition of conc. hydrochloric acid and the mixture was then heated to 70° C. for 2 hr. The mixture was cooled to RT and was concentrated in vacuo to ca 20 mL and then diluted with water (30 mL). The aq. mixture was adjusted to pH12 by the addition of aq NaOH solution (6M) and was then extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine (30 mL) and then dried (MgSO4) and evaporated in vacuo to afford the title compound as a brown oil (1.78 g, 90% pure, 72%); Rt 1.32 min (Method 2); m/z 216 (M+H)+ (ES+). This material was used directly in the next step, without further purification.

Provenance & Evidence