Methyl iodide → 1H-Pyrazole-4-carboxylic acid, 1-(2-hydroxyethyl)-5-methyl-, ethyl ester

HRID 2070963Notes

Reaction equation

HRID 2070963 reaction equation
CCN(/C=C(/C(OCC)=O)\[C:8](C)=[O:9])CC.OCCNN.[C:21]([N:25]1[C:29]([CH3:30])=[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:27]=[N:26]1)(C)(C)[CH3:22].[H-].[Na+].[OH:38][CH2:39][CH2:40][N:41]1[C:45]([CH3:46])=[C:44]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH:43]=[N:42]1.CI>C1COCC1>[OH:38][CH2:39][CH2:40][N:41]1[C:45]([CH3:46])=[C:44]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH:43]=[N:42]1.[CH3:8][O:9][CH2:22][CH2:21][N:25]1[C:29]([CH3:30])=[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:27]=[N:26]1

Participants

9

Reactant 6

HCID 6328Methyl iodideHCID 80172-HydrazinoethanolHCID 24758Sodium hydrideHCID 11424414HCID 11424414, compoundHCID 13654177ethyl 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylateHCID 336776011H-Pyrazole-4-carboxylic acid, 1-(2-hydroxyethyl)-5-methyl-, ethyl ester

Product 2

HCID 336776011H-Pyrazole-4-carboxylic acid, 1-(2-hydroxyethyl)-5-methyl-, ethyl esterYield 67%HCID 68670765HCID 68670765, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 1-(2-hydroxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (376 mg, 67%) was synthesized from diethylaminomethylene ethyl acetoacetate (509 mg, 2.8 mmol) and 2-hydroxyethyl hydrazine (0.30 mL, 4.1 mmol) following the general procedure for ethyl 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylate as described (see R. A. Fecik, P. Devasthale, S. Pillai, A. Keschavarz-Shokri, L. Sehn, and L. A. Mitscher; J. Med. Chem. 2005, 48, 122). To a stirred solution of NaH (91 mg, 2.3 mmol) in THF (5 mL) was added ethyl 1-(2-hydroxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (376 mg, 1.9 mmol) in THF (1 mL) at 0° C. followed by MeI (0.18 mL, 2.9 mmol). The resulting mixture was stirred for 15 h and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous layer was extracted with EtOAc (3×3 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduce pressure. The residue was purified by column chromatography to provide ethyl 1-(2-methoxyethyl)-5-methyl-1H-pyrazole-4-carboxylate (249 mg, 62%) as a yellow oil.

Workup

  1. customquenched with saturated aqueous NH4Cl
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (3×3 mL)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-379e50f97bea4bd887fc008eefa101d9
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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