Reaktion #58952

Reaktionsgleichung

sodium hydroxide

5-(4-fluorophenyl)-1-methyl-1H-pyrazole-4-carbaldehyde

malonic acid

piperidine

→

(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]acrylic acid

Ausbeute 90.0%

Lösungsmittel

toluene

bis(2-methoxyethyl) ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITand further at 105-110° C. for 4 hrs
2. 2
   TemperaturAfter cooling to 25° C.
3. 3
   workup.STIRRINGthe mixture was stirred
4. 4
   SonstigeThe aqueous layer was separated
5. 5
   Extraktionthe organic layer was extracted with 1N aqueous sodium hydroxide solution (6 mL)
6. 6
   Waschenwashed with toluene
7. 7
   Sonstigewere adjusted to pH 3.5-4.0 with 2N hydrochloric acid at 20-30° C.
8. 8
   workup.ADDITIONwater (9 mL) was added dropwise
9. 9
   workup.STIRRINGAfter stirring at 25° C. for 1 hr
10. 10
    Filtration, the precipitated crystals were collected by filtration
11. 11
    Waschenwashed with 20% ethanol

Vorschrift

To a mixture of 5-(4-fluorophenyl)-1-methyl-1H-pyrazole-4-carbaldehyde (3.00 g), malonic acid (1.99 g) and bis(2-methoxyethyl) ether (9 mL) was added dropwise piperidine (1.89 mL) over about 10 min. The mixture was stirred at 90-95° C. for 1 hr. and further at 105-110° C. for 4 hrs. After cooling to 25° C., toluene (12 mL) and 1N aqueous sodium hydroxide solution (15 mL) were added and the mixture was stirred. The aqueous layer was separated and the organic layer was extracted with 1N aqueous sodium hydroxide solution (6 mL). The aqueous layers were combined and washed with toluene. The layers were adjusted to pH 3.5-4.0 with 2N hydrochloric acid at 20-30° C. and water (9 mL) was added dropwise. After stirring at 25° C. for 1 hr., the precipitated crystals were collected by filtration and washed with 20% ethanol to give (2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]acrylic acid (3.24 g, yield 90%).

Quelle