Reaction #65196

Reaction equation

compound

4-(4-Fluorophenyl)-6-isopropyl-2-methoxy-3-methoxymethyl-pyridine-5-carbaldehyde

tetrahydrofuran

tetrahydrofuran

oxalic acid dihydrate

sodium hydride

tetrahydrofuran

→

(E)-3-[4-(4-Fluorophenyl)-6-isopropyl-2-methoxy-3-methoxymethyl-pyridin-5-yl]-prop-2-enal

Solvents

water

Conditions

Workup

1. 1
   Temperaturethe mixture is heated
2. 2
   Temperatureto reflux for 30 min
3. 3
   Extractionextracted three times
4. 4
   WashThe combined organic phases are washed with saturated sodium chloride solution
5. 5
   Dryingdried over sodium sulphate
6. 6
   ConcentrationAfter concentration in vacuo
7. 7
   Temperatureheated
8. 8
   Temperatureto reflux for 90 min
9. 9
   TemperatureAfter cooling to room temperature
10. 10
    Otherthe phases are separated
11. 11
    Washthe organic phase is washed with saturated sodium chloride solution
12. 12
    Dryingdried over sodium sulphate
13. 13
    Concentrationconcentrated in vacuo
14. 14
    workup.DISSOLUTIONThe residue is dissolved in methylene chloride
15. 15
    Filtrationfiltered through silica gel

Procedure

804 (3.1 mmol) of diethyl 2-(cyclohexylamino)-vinyl-phosphate dissolved in 6 ml of dry tetrahydrofuran are added dropwise under nitrogen to a suspension of 59 mg (2.5 mmol) of sodium hydride in 6 ml of dry tetrahydrofuran at -5° C. After 30 min, 0.65 g (2.05 mmol) of the compound from Example 9 in 15 ml of dry tetrahydrofuran is added dropwise at the same temperature and the mixture is heated to reflux for 30 min. After cooling to room temperature, the mixture is added to 200 ml of ice-cold water and extracted three times using 100 ml of ethyl acetate each time. The combined organic phases are washed with saturated sodium chloride solution and dried over sodium sulphate. After concentration in vacuo, the residue is taken up in 5 ml of toluene, treated with a solution of 0.9 g (7 mmol) of oxalic acid dihydrate in 12 ml of water and heated to reflux for 90 min. After cooling to room temperature, the phases are separated, and the organic phase is washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is dissolved in methylene chloride and filtered through silica gel.

Source