Acetic Acid → 3-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole

HRID 1607215Notes

Reaction equation

HRID 1607215 reaction equation
[CH3:1][C:2]([CH2:16]OS(C)(=O)=O)([C:7]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)=O)[C:3]([O:5][CH3:6])=[O:4].C(O)(=O)C.C([O-])(=O)C.[Na+].O.[NH2:32][NH2:33].[OH-].[Na+]>C(OCC)C.O.CO>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:7]2[C:2]([C:3]([O:5][CH3:6])=[O:4])([CH3:1])[CH2:16][NH:33][N:32]=2)=[CH:10][CH:11]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 517045Sodium AcetateHCID 19852270Methyl 2-methyl-2-mesyloxymethyl-3-(4-chlorophenyl)-3-keto-propanoate

Product 1

HCID 198521233-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

Into a 5 liter RBF was added 700 g (2.07) mole) of methyl 2-methyl-2-mesyloxymethyl-3-(4-chlorophenyl)-3-keto-propanoate and 1700 ml of methanol. The slurry is warmed to 50° C. whereon, 248 g (4.14 mole) of acetic acid and 186 g (2.28 mole) of sodium acetate are added. Without further heating, 207 g (4.14 mole) of hydrazine hydrate is added over 20 minutes and the temperature is allowed to rise to reflux. After the addition, the mixture is allowed to stir for 45 minutes whereon the temperature has fallen 50° C. The mixture is worked up with 2 kgs of ice, 2 kgs of cold water and 5 liters of ethyl ether and neutralized using approximately 300 g of 50% NaOH to achieve pH 8. After separating the organic layer and washing it with brine the organic layer is thoroughly dried with MgSO4. The resulting solution of 3-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole is used as is in the next reaction. NMR data was consistent with the structure.

Workup

  1. additionare added
  2. temperatureto reflux
  3. additionAfter the addition
  4. customhas fallen 50° C
  5. customAfter separating the organic layer
  6. washwashing it with brine the organic layer
  7. dry with materialis thoroughly dried with MgSO4
  8. customas is in the next reaction

Sources & evidence

ORD record
ord-e05b96288dd64750a990610e1ba497ae
Source dataset
uspto-grants-1989_09
Patent number
US04863947

Reaction notes

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