Ethyl 2-acetyl-3-(dimethylamino)acrylate → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid ethyl ester

HRID 219659Notes

Reaction equation

HRID 219659 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([NH2:8])=[NH:7].[CH2:12]([O:14][C:15](=[O:24])[C:16](=[CH:20]N(C)C)[C:17](=O)[CH3:18])[CH3:13]>CCO>[CH2:12]([O:14][C:15]([C:16]1[C:17]([CH3:18])=[N:7][C:6]([C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([F:2])[CH:4]=2)=[N:8][CH:20]=1)=[O:24])[CH3:13]

Participants

4

Reactant 2

HCID 3806790Ethyl 2-acetyl-3-(dimethylamino)acrylateHCID 124561593-Fluorobenzene-1-carboximidamide--hydrogen chloride (1/1)

Product 1

HCID 685575422-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid ethyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Na° (0.66 g, 28.6 mmol) is added to anhydrous EtOH (100 mL) and stirred at room temperature for 15 min. 3-Fluorobenzamidine hydrochloride (4.87 g, 27.8 mmol) is added and the solution is stirred for 15 min. 2-Dimethylaminomethylene-3-oxo-butyric acid ethyl ester (5.3 g, 28.6 mmol,) is added and the reaction mixture is heated at reflux under N2 for 1 hours. The reaction is cooled to room temperature and concentrated in vacuo. The residue is dissolved in EtOAc (300 mL), washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid ethyl ester (6.8 g, 99%). MS: 261 (M+H); 1H NMR (300 MHz, CDCl3): δ 1.43 (t, J=7.0 Hz, 3H), 2.92 (s, 3H), 4.42 (q, J=7.0 Hz, 2H), 7.24 (m, 1H), 7.45 (m, 1H), 8.27 (m, 1H), 8.37 (m, 1H), 9.21 (s, 1H).

Workup

  1. stirringthe solution is stirred for 15 min
  2. temperaturethe reaction mixture is heated
  3. temperatureat reflux under N2 for 1 hours
  4. temperatureThe reaction is cooled to room temperature
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in EtOAc (300 mL)
  7. washwashed with brine (2×100 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9069365320e14d26bf2dfa5f51f237ed
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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