Sodium hydride → 4-Ethoxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl ester

HRID 645745Notes

Reaction equation

HRID 645745 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:16])=[N:8][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].[CH2:17](OC(C1C(O)=NC(CC)=NC=1)=O)[CH3:18].[H-].[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:16][CH2:17][CH3:18])=[N:8][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 178469768HCID 178469768, compoundHCID 178469771HCID 178469771, compound

Product 1

HCID 672066074-Ethoxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-hydroxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl ester (3 g, 13.377 mmol, prepared in an analogous manner as described for the preparation of 2-ethyl-4-hydroxy-pyrimidine-5-carboxylic acid ethyl ester, Dostert, P. et al. Eur. J. Med. Chem. 1982, 17, 437-444) in dimethylformamide (10 mL) was added slowly to the suspension of sodium hydride (800 mg, 60% in mineral oil, Aldrich) in dimethylformamide cooled to 0° C. After the addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was stirred at room temperature for 4 h then quenched with saturated solution of ammonium chloride. It was extracted with ethyl acetate (2×). The organic extracts were washed with brine (1×), dried over anhydrous sodium sulfate and concentrated. Purification of the crude residue by flash column chromatography (120 g of silica gel, eluting with a gradient of 5-60% ethyl acetate in hexane gave 4-ethoxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl ester (1.12 g, 30%).

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringThe reaction mixture was stirred at room temperature for 4 h
  4. customthen quenched with saturated solution of ammonium chloride
  5. extractionIt was extracted with ethyl acetate (2×)
  6. washThe organic extracts were washed with brine (1×)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customPurification of the crude residue by flash column chromatography (120 g of silica gel
  10. washeluting with a gradient of 5-60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-82890cbca6504ca58eb4692ddea876d0
Source dataset
uspto-grants-2010_04
Patent number
US07705007B2

Reaction notes

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