Ethanol → ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoate

HRID 1296828Notes

Reaction equation

HRID 1296828 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[N:11]=[C:10]([CH2:21][CH2:22][C:23]([OH:25])=[O:24])[CH:9]=2)=[CH:4][CH:3]=1.[CH2:26](O)[CH3:27].OS(O)(=O)=O.CCCCCC>CO.C(OC(=O)C)C>[CH2:26]([O:24][C:23](=[O:25])[CH2:22][CH2:21][C:10]1[CH:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:11]=1)[CH3:27]

Participants

7

Reactant 4

HCID 702EthanolHCID 1118Sulfuric AcidHCID 8058HexaneHCID 1888503-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]propanoic Acid

Product 1

HCID 11222871ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoateYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoic acid (300 g, 840 mmol) and ethanol (3 L) were placed in a flask. Concentrated H2SO4 (2.4 mL, 86.4 meq.) was added with stirring. The reaction was then heated to reflux. After approximately 30 minutes, the suspension dissolved. The reaction was monitored by TLC (silica gel; hexane:ethylacetate:methanol;70:20:10). After refluxing for 9 hours, all starting material was gone and 2 liters of ethanol was removed by distillation. The remaining solution was cooled with stirring to 0° C. and seeded with known ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoate. The resulting suspension was stirred at 0° C. for 30 minutes and then filtered, washed with cold ethanol (100 mL) and vacuum dried (room temperature, ca. 5 mm Hg) to give ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoate (275.0 g, 85% yield) as a clean white powder (mp=80-81° C.). An additional 27.9 9 of ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoate was obtained as a tan powder after reducing the volume of the mother liquor to approximately 100 mL and seeding with known ethyl-5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-propanoate.

Workup

  1. temperatureThe reaction was then heated to reflux
  2. dissolutionthe suspension dissolved
  3. temperatureAfter refluxing for 9 hours
  4. custom2 liters of ethanol was removed by distillation
  5. temperatureThe remaining solution was cooled
  6. stirringwith stirring to 0° C.
  7. stirringThe resulting suspension was stirred at 0° C. for 30 minutes
  8. filtrationfiltered
  9. washwashed with cold ethanol (100 mL) and vacuum
  10. customdried (room temperature, ca. 5 mm Hg)

Sources & evidence

ORD record
ord-f37be7e07dc64232927d05625e986bc7
Source dataset
uspto-grants-2007_07
Patent number
US07247745B2

Reaction notes

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