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

HRID 1692697Notes

Reaction equation

HRID 1692697 reaction equation
[CH3:1][CH:2]([CH2:6][C:7](=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3](O)=[O:4].O.[NH2:16][NH2:17]>C(O)C>[CH3:1][CH:2]1[CH2:6][C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:17][NH:16][C:3]1=[O:4]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 744922-Methyl-4-oxo-4-phenylbutanoic acid

Product 1

HCID 139013904-Methyl-6-phenyl-4,5-dihydropyridazin-3(2H)-oneYield 96.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

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 et al. Journal of Heterocyclic Chemistry, 1988, 25(3), 799-802.]

Workup

  1. temperatureThe suspension is cooled to below 10° C.
  2. customat below 20° C
  3. additionUpon addition
  4. additionAfter addition
  5. temperaturethe reaction mixture is heated
  6. temperatureto reflux
  7. temperatureafter 20 minutes of heating
  8. customthe flask is removed from the oil bath
  9. temperatureUpon cooling
  10. filtrationwhite crystals form in the flask, which are collected by filtration
  11. washThe solid is washed first with 30 mL of 2N NaHCO3
  12. customdried over a medium frit sintered glass funnel in vacuo

Sources & evidence

ORD record
ord-5f60f0bb05f24cfaa252d1552095fdc9
Source dataset
uspto-grants-2012_04
Patent number
US08158627B2

Reaction notes

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