Sodium hydride → methyl 5-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-3-carboxylate

HRID 513178Notes

Reaction equation

HRID 513178 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][N:6]=1)=[O:4].[H-].[Na+].[CH3:18][Si:19]([CH2:22][CH2:23][O:24][CH2:25]Cl)([CH3:21])[CH3:20]>C1COCC1.CCOC(C)=O>[C:10]1([C:8]2[N:7]([CH2:25][O:24][CH2:23][CH2:22][Si:19]([CH3:21])([CH3:20])[CH3:18])[N:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:9]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178497263HCID 178497263, compound

Product 1

HCID 71212623methyl 5-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-3-carboxylateYield 92.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-phenyl-1H-pyrazole-3-carboxylic acid methyl ester (250 mg, 1.236 mmole) in THF (5 mL) was added NaH (60% dispersion in mineral oil, 60 mg, 1.500 mmole) portionwise at RT. After gas evolution had ceased SEMCl (0.263 mL, 1.484 mmol) was added. After stirring overnight the mixture was diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. Flash column (Biotage-SNAP-25 g SiO2, 0-20% EtOAc/hexanes) gave methyl 5-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-3-carboxylate (380 mg, 92%) as a clear oil. 1H NMR (399 MHz, CDCl3): δ 7.64 (dd, J=7.3, 1.9 Hz, 3 H); 7.46 (d, J=7.4 Hz, 3 H); 6.94 (s, 1 H); 5.49 (s, 2 H); 3.96 (s, 3 H); 3.80-3.71 (m, 3 H); 0.97-0.88 (m, 2 H); 0.02 (s, 9H).

Workup

  1. additionwas added
  2. filtrationfiltered through a pad of Celite
  3. washwashing with EtOAc
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8db08e12454c463892628cf8e3bb07e3
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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