Hydrazine hydrate (1:1) → 4-Methyl-6-phenyl-4,5-dihydropyridazin-3(2H)-one

Participants

Reaction Steps

A 250 mL three-neck round bottom flask fit with a temperature probe and condenser is charged with 7.7 g (40 mmole) of 2-methyl-4-oxo-4-phenylbutanoic acid 1 and 20 ml of ethanol (95%). The suspension is cooled to below 10° C. and 2.2 ml (42 mmole, 1.05 equiv.) of hydrazine monohydrate in 10 mL of ethanol is added dropwise at a rate that maintains the solution temperature at below 20° C. Upon addition, the suspension changes to a pale yellow solution. After addition, the reaction mixture is heated to reflux and stirred for 2 h, and after 20 minutes of heating, a solid is seen in the mixture. Once the reaction is completed, the flask is removed from the oil bath and cooled to ambient temperature. Upon cooling, white crystals form in the flask, which are collected by filtration. The solid is washed first with 30 mL of, 2N NaHCO3, followed by 60 mL Milli-Q water three times, and dried over a medium frit sintered glass funnel in vacuo to give the desired product 2 in 96.1% yield. [See Hansen, K B et al. Organic process research & development, 2005, 9, 634-639; Nelson, D A. US 20050137397A1. Coudert, P at al. Journal of Heterocyclic Chemistry, 1988, 25(3), 799-802.]

Provenance & Evidence