Hydrochloric Acid → Ethyl 2-(5-bromo-2-nitrophenyl)-3-(4-fluorophenyl)-3-hydroxyacrylate

HRID 44015

Reaktionsgleichung

Reaktionsgleichung von HRID 44015
C(=O)([O-])[O-].[K+].[K+].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10](F)[CH:9]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25](=[O:32])[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:21][CH:20]=1.Cl>CS(C)=O>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([C:26](=[C:25]([C:22]2[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=2)[OH:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:9]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2758844Ethyl 3-(4-Fluorophenyl)-3-OxopropanoateHCID 27833624-Bromo-2-fluoro-1-nitrobenzene

Produkt 1

HCID 59233779Ethyl 2-(5-bromo-2-nitrophenyl)-3-(4-fluorophenyl)-3-hydroxyacrylateAusbeute 105 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Versuchsvorschrift

Potassium carbonate (3.3 g, 24 mmol) was added to a stirred solution of 4-bromo-2-fluoro-1-nitrobenzene (2.45 g, 11 mmol) and ethyl 3-(4-fluorophenyl)-3-oxopropanoate (2.7 g, 13 mmol) in DMSO (11 mL). The yellow solution turned purple and the reaction was stirred at r.t. After 8 h, the reaction was neutralized with 25 mL of 1N HCl and extracted with EtOAc. The organic phase was washed with water (×3) and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography on a Biotage 40+M column (gradient elution 5% to 25% EtOAc/hexanes over 10 column volumes, fraction collection at μ, =254 nm) to afford the title compound as a viscous amber oil, 4.8 g (105% yield, contains ˜10 weight % EtOAc by 1H NMR). 1H NMR (˜0.6:1 ratio of keto:enol tautomers, 500 MHz, CDCl3) δ ppm 13.47 (s, 1H) 7.94-8.05 (m, 2H) 7.86 (d, J=8.55 Hz, 1 H) 7.62-7.72 (m, 1.2 H) 7.51 (dd, J=8.55, 2.14 Hz, 1H) 7.29-7.35 (m, 2H) 7.15-7.21 (m, 1.2 H) 7.12 (d, J=2.14 Hz, 1H) 6.94 (t, J=8.55 Hz, 2H) 6.35 (s, 0.6 H) 4.20-4.34 (m, 2H) 4.04-4.11 (m, 1.2 H) 1.23-1.27 (m, 2H) 1.18 (t, J=7.17 Hz, 3 H). LC/MS was performed on a Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=5% CH3CN/95% H2O/10 mM NH4OAc, solvent B=95% CH3CN/5% H2O/10 mM NH4OAc, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=5 ml/min, column: XBridge C18 5 μm 4.6×50 mm; 2 peaks elute with HPLC Rt=1.69 and 1.83 min (˜1:2 ratio), (ES−) m/z (M−) for both=408, 410 (1:1 ratio).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with water (×3) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography on a Biotage 40+M column (gradient elution 5% to 25% EtOAc/hexanes over 10 column volumes, fraction collection at μ, =254 nm)

Quellen und Nachweise

ORD-Eintrag
ord-d55b97acb55047e8b72401ea64b400f6
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536338B2

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