Ethanol → 1-(5-Bromo-2-hydroxy-benzyl)-5-methyl-1H-pyrazole-4-carboxylic acid methyl ester

HRID 575934Notes

Reaction equation

HRID 575934 reaction equation
C(O[C:6]([NH:8][NH:9][CH2:10][C:11]1[CH:16]=[C:15]([Br:17])[CH:14]=[CH:13][C:12]=1[OH:18])=O)(C)(C)C.CCO.[CH3:22][O:23][C:24](=[O:33])/[C:25](=C\N(C)C)/[C:26](=O)[CH3:27]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:22][O:23][C:24]([C:25]1[CH:6]=[N:8][N:9]([CH2:10][C:11]2[CH:16]=[C:15]([Br:17])[CH:14]=[CH:13][C:12]=2[OH:18])[C:26]=1[CH3:27])=[O:33]

Participants

6

Reactant 3

HCID 702EthanolHCID 17874501Methyl 2-[(dimethylamino)methylene]acetoacetateHCID 57875608HCID 57875608, compound

Product 1

HCID 896466631-(5-Bromo-2-hydroxy-benzyl)-5-methyl-1H-pyrazole-4-carboxylic acid methyl esterYield 18.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A suspension of N′-(5-bromo-2-hydroxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester 1 2 g (6.3 mmol) in a mixture of CH2Cl2 (8 mL) and TFA (8 mL) was stirred at RT for 2 hours. The volatiles were removed in vacuo. The residue was dissolved in abs. EtOH (7 mL) and added to 2-[1-Dimethylamino-meth-(Z)-ylidene]-3-oxo-butyric acid methyl ester (12 mmol) at RT. The resulting mixture was stirred at RT for 1 hour, refluxed for 2 h, let cool down and stirred at RT for 16 h. The oily residue obtained after removing the volatiles in vacuo was purified by MPLC (10 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc) to give 0.38 g of 1-(5-Bromo-2-hydroxy-benzyl)-5-methyl-1H-pyrazole-4-carboxylic acid methyl ester, 5 and 1-(5-Bromo-2-hydroxy-benzyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester 6 as a mixture.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in abs
  3. stirringThe resulting mixture was stirred at RT for 1 hour
  4. temperaturerefluxed for 2 h
  5. temperaturelet cool down
  6. stirringstirred at RT for 16 h
  7. customThe oily residue obtained
  8. customafter removing the volatiles in vacuo
  9. customwas purified by MPLC (10 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc)

Sources & evidence

ORD record
ord-9c32fef9f18041ea969948202d00df32
Source dataset
uspto-grants-2015_05
Patent number
US09035071B2

Reaction notes

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