Sodium hydride → 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl ester

HRID 230171Notes

Reaction equation

HRID 230171 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][NH:8][N:7]=1)=[O:5])[CH3:2].[H-].[Na+].[CH3:16][Si:17]([CH3:24])([CH3:23])[CH2:18][CH2:19][O:20][CH2:21]Cl>CN(C)C=O.C(OCC)(=O)C.O>[N+:11]([C:10]1[CH:9]=[N:8][N:7]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:24])([CH3:23])[CH3:16])[C:6]=1[C:4]([O:3][CH2:1][CH3:2])=[O:5])([O-:13])=[O:12].[N+:11]([C:10]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[N:7][N:8]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:24])([CH3:23])[CH3:16])[CH:9]=1)([O-:13])=[O:12]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178470496HCID 178470496, compound

Product 2

HCID 866004844-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl esterHCID 1317270884-nitro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-3-carboxylic acid, ethyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 0° C. solution of 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester (6.4 g, 34.58 mmol) in dimethylformamide (80 mL) was added sodium hydride (2.07 g, 1.5 eq), and the resulting mixture was stirred from 0° C. to room temperature for one hour. To this mixture was added 2-(trimethylsilyl)ethoxy-methyl chloride (Aldrich) (9.17 mL, 1.5 eq), and the resulting mixture was stirred at room temperature for 2 days. The reaction was monitored by TLC. The reaction mixture was diluted with ethyl acetate (300 mL) and water (100 mL). the organic layer was separated, washed with water (6×100 mL) and brine (1×100 mL), dried over magnesium sulfate, filtered and concentrated to give 10 g of the crude product. Purification by column chromatography using 5% ethyl acetate in hexanes afforded 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl ester (3.82 g) as a colorless oil and 4-nitro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-3-carboxylic acid, ethyl ester (4.055 g) as a light tan oil. (M−H)+=314.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 2 days
  2. customthe organic layer was separated
  3. washwashed with water (6×100 mL) and brine (1×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give 10 g of the crude product
  8. customPurification by column chromatography

Sources & evidence

ORD record
ord-ad56931cd30e4a158332b5baa6ec8583
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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