Potassium Phosphate, Tribasic → 5-methyl-1-(4-vinylphenyl)-1H-pyrazole-4-carboxylic acid

HRID 1748440Notes

Reaction equation

HRID 1748440 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[C:10]=1[CH3:11])=[O:5])C.[CH:19]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCC[CH2:20]1.C(B1OC(C)(C)C(C)(C)O1)=C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCCC1>[CH3:11][C:10]1[N:9]([C:12]2[CH:13]=[CH:14][C:15]([CH:19]=[CH2:20])=[CH:16][CH:17]=2)[N:8]=[CH:7][C:6]=1[C:4]([OH:3])=[O:5]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 3470813ethyl 1-(4-bromophenyl)-5-methyl-1H-pyrazole-4-carboxylateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 866924095-methyl-1-(4-vinylphenyl)-1H-pyrazole-4-carboxylic acidYield 461.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Tetrahydrofuran (10 ml) was added to 1-(4-bromophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.5 g) described in Reference Example 26(1), palladium (II) acetate (108 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (198 mg), vinylboronic acid pinacol ester (1.04 g) and tripotassium phosphate (2.6 g), and stirred at 100° C. for 7 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). 4N Aqueous solution of sodium hydroxide (4 ml) and ethanol (10 ml) were added to the purified yellow oily product, stirred at 80° C. for two hours and the reaction solution was washed with ethyl acetate. 1N Hydrochloric acid aqueous solution was added to the aqueous layer at 0° C., and the precipitated solid was washed with diethyl ether and water to give 5-methyl-1-(4-vinylphenyl)-1H-pyrazole-4-carboxylic acid (508 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. washthe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
  6. addition4N Aqueous solution of sodium hydroxide (4 ml) and ethanol (10 ml) were added to the purified yellow oily product
  7. stirringstirred at 80° C. for two hours
  8. washthe reaction solution was washed with ethyl acetate
  9. addition1N Hydrochloric acid aqueous solution was added to the aqueous layer at 0° C.
  10. washthe precipitated solid was washed with diethyl ether and water

Sources & evidence

ORD record
ord-4e321b0293e84de78c5f033c550adcf7
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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