Reaktion #472502

Reaktionsgleichung

2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester

→

2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid

Ausbeute 64.7%

Lösungsmittel

AcOH H2O EtOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was heated
2. 2
   Temperaturunder reflux for 96 h
3. 3
   TemperaturAfter cooling the solvent
4. 4
   Sonstigewas evaporated under reduced pressure and water (200 mL)
5. 5
   workup.ADDITIONwas added
6. 6
   ExtraktionThe reaction mixture was extracted with EtOAc (3×100 mL)
7. 7
   Waschenthe combined extracts were washed with water (3×100 mL), brine (100 mL)
8. 8
   Trocknendried (MgSO4)
9. 9
   SonstigeEvaporation of solvent under reduced pressure
10. 10
    Sonstigegave a yellow oil which
11. 11
    Sonstigecrystallized

Vorschrift

The above 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester (57.0 g, 152.8 mmol) was dissolved in AcOH/H2O/EtOH (400 mL/120 mL/50 mL) and the reaction mixture was heated under reflux for 96 h. After cooling the solvent was evaporated under reduced pressure and water (200 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined extracts were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave a yellow oil which crystallized on standing to yield 27 g of 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid. Chromatography of the residual oil (Heptane-EtOAc gradient) gave an additional 3 g of product (72% combined yield). 1H NMR (300 MHz, CDCl3/TMS): δ 9.63 (br s, 1H), 7.82 (dd, J=8.8, 6.0 Hz, 1H), 7.38 (dd, J=11.0, 5.8 Hz, 1H), 4.14-4.08 (m, 1H), 2.05-1.95 (m, 1H), 1.76-1.66 (m, 1H), 1.52-1.43 (m, 1H), 0.95-0.92 (m, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 177.6, 158.2 (d, 1JCF=232.5 Hz), 150.9 (d, 1JCF=262.5 Hz), 136.0, 134.7, 119.0 (d, 2JCF=20.0, Hz), 113.1 (d, 2JCF=29.4 Hz), 41.7, 41.3, 26.0, 22.6, 21.9.

Quelle