Reaktion #472501

Reaktionsgleichung

2-Isobutylmalonic acid diethyl ester

sodium hydride

1,2,4-trifluoro-5-nitro-benzene

→

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

Ausbeute 90.1%

Lösungsmittel

DMF

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled to 0° C.
2. 2
   SonstigeThe resulting reaction mixture
3. 3
   workup.STIRRINGwas stirred at room temperature for 16 h
4. 4
   Extraktionextracted with EtOAc (3×100 mL)
5. 5
   WaschenThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
6. 6
   Trocknendried (MgSO4)
7. 7
   SonstigeEvaporation of solvent under reduced pressure
8. 8
   Sonstigegave a brown oil which
9. 9
   Sonstigewas purified by column chromatography over silica gel (Heptane-EtOAc, gradient)

Vorschrift

2-Isobutylmalonic acid diethyl ester (40.0 g, 0.185 mol) in DMF (50 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 8.0 g, 0.33 mol) in 200 mL DMF (200 mL) over 20 min. at 0° C. under nitrogen. The mixture was stirred for 0.5 h at room temperature, cooled to 0° C. and 1,2,4-trifluoro-5-nitro-benzene (30.0 g, 169.5 mmol) in DMF (150 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 16 h, poured into ice water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave a brown oil which was purified by column chromatography over silica gel (Heptane-EtOAc, gradient) to give 57.0 g (90%) of 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester as yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.87 (dd, J=12.3, 6.0 Hz, 1H), 7.79 (dd, J=10.1, 6.4 Hz, 1H), 4.30-4.18 (m, 4H), 2.27 (d, J=5.8 Hz, 2H), 1.60-1.50 (m, 1H), 1.26 (t, J=7.1 Hz, 6H), 0.82 (d, J=7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 168.2, 155.1 (d, 1JCF=252.3 Hz), 150.9 (d, 1JCF=263.2 Hz), 135.7, 135.1, 120.0 (dd, 2JCF=26.0, 3JCF=4.0 Hz), 113.0 (d, 2JCF=29.0 Hz), 62.3, 43.1, 24.9, 23.8, 13.8.

Quelle