Methyl formate → 4-Ethoxy-6-(trifluoromethyl)pyrimidine-5-carbaldehyde

HRID 254219Notes

Reaction equation

HRID 254219 reaction equation
Br[C:2]1[C:3]([O:12][CH2:13][CH3:14])=[N:4][CH:5]=[N:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C([Li])CCC.[CH:20](OC)=[O:21].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[CH2:13]([O:12][C:3]1[C:2]([CH:20]=[O:21])=[C:7]([C:8]([F:11])([F:10])[F:9])[N:6]=[CH:5][N:4]=1)[CH3:14]

Participants

7

Reactant 4

HCID 7865Methyl formateHCID 25517Ammonium ChlorideHCID 178628775-Bromo-4-ethoxy-6-trifluoromethylpyrimidineHCID 178418339Butyllithium

Product 1

HCID 178628784-Ethoxy-6-(trifluoromethyl)pyrimidine-5-carbaldehydeYield 81.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5.76 g (21.3 mmoles) of 5-bromo-4-ethoxy-6-trifluoromethylpyrimidine dissolved in 250 ml of tetrahydrofuran was cooled to −78° C. Thereinto was dropwise added 22.6 ml of a 1.6 M hexane solution containing 36.1 mM of n-butyl lithium. The mixture was stirred for 40 minutes. Thereto was added 2.7 g (45.1 mmoles) of methyl formate. The mixture was stirred for 1.5 hours to give rise to a reaction. After the completion of the reaction, an aqueous ammonium chloride solution was added and extraction with ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate mixed solvent) to obtain 3.82 g (yield: 81.6%) of 4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.

Workup

  1. stirringThe mixture was stirred for 1.5 hours
  2. customto give rise
  3. customto a reaction
  4. customAfter the completion of the reaction
  5. extractionextraction with ether
  6. washThe resulting organic layer was washed with an aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe resulting solution was subjected to reduced pressure distillation
  9. customto remove the solvent
  10. customThe residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate mixed solvent)

Sources & evidence

ORD record
ord-01c14bba01f0430f82fdd1b7ba0c7b21
Source dataset
uspto-grants-2011_01
Patent number
US07875606B2

Reaction notes

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