Diisopropylamine → ethyl 3-(cyclopropanecarbonyl)-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate

HRID 1520220Notes

Reaction equation

HRID 1520220 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.[CH3:21][O:22][C:23]1[CH:39]=[CH:38][C:26]([CH2:27][N:28]2[CH:32]=[C:31]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:30]=[N:29]2)=[CH:25][CH:24]=1.CON(C)[C:43]([CH:45]1[CH2:47][CH2:46]1)=[O:44]>C1COCC1.CCOC(C)=O>[CH:45]1([C:43]([C:30]2[C:31]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:32][N:28]([CH2:27][C:26]3[CH:25]=[CH:24][C:23]([O:22][CH3:21])=[CH:39][CH:38]=3)[N:29]=2)=[O:44])[CH2:47][CH2:46]1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 15643267N-Methoxy-N-methylcyclopropanecarboxamideHCID 44558860ethyl 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67432976ethyl 3-(cyclopropanecarbonyl)-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylateYield 9.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

According to Scheme 16: Butyl lithium 2.5 M (9.9 mmol, 4 mL) was added to a solution of diisopropylamine (9.9 mmol, 1.4 mL) in THF (20 mL) at −78° C. and the reaction mixture was stirred at −78° C. for 5 minutes and then at room temperature. To the resulting LDA solution was added at −78° C. a solution of ethyl 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate (7.61 mmol, 1.98 g) in THF (30 mL) and the reaction mixture was stirred for 15 minutes at −78° C. Then N-methoxy-N-methylcyclopropanecarboxamide (9.14 mmol, 1.18 g) in THF (10 mL) was added and the reaction mixture was stirred at room temperature. The reaction mixture was diluted with AcOEt and washed with a saturated aqueous solution of NH4Cl. The combined organic phases were dried over MgSO4, were filtered and solvents were evaporated. The crude mixture was purified by flash chromatography over silica gel using cyclohexane/AcOEt (90:10) as eluent to yield ethyl 3-(cyclopropanecarbonyl)-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate (0.74 mmol, 244 mg, 9%).

Workup

  1. customat room temperature
  2. stirringthe reaction mixture was stirred for 15 minutes at −78° C
  3. stirringthe reaction mixture was stirred at room temperature
  4. washwashed with a saturated aqueous solution of NH4Cl
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationwere filtered
  7. customsolvents were evaporated
  8. customThe crude mixture was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-a7f3b950de5941e197810b8613707ade
Source dataset
uspto-grants-2015_07
Patent number
US09073907B2

Reaction notes

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