Isopropanol → HCID 89942768, Verbindung

HRID 541054Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 541054
ClC1C(Cl)=C(C2C=CC=CC=2)N=C(C(Cl)=O)C=1.[F-].[K+].[F:20][C:21]1[C:26]([F:27])=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:24]=[C:23]([C:34](F)=[O:35])[CH:22]=1.C(N(CC)CC)C.[CH:44]([OH:47])([CH3:46])[CH3:45]>S1(CCCC1)(=O)=O.O>[F:20][C:21]1[C:26]([F:27])=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:24]=[C:23]([C:34]([O:47][CH:44]([CH3:46])[CH3:45])=[O:35])[CH:22]=1

Komponenten

8

Edukt 5

HCID 3776IsopropanolHCID 8471TriethylamineHCID 522689Potassium FluorideHCID 86709875HCID 86709875, VerbindungHCID 89943386HCID 89943386, Verbindung

Produkt 1

HCID 89942768HCID 89942768, VerbindungAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 31347SulfolaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

To a solution of 4,5-dichloro-6-phenylpicolinoyl chloride (1.76 g, 6.14 mmol) in sulfolane (40 mL, dried over 4 Å molecular sieves, ˜100 ppm H2O) was added potassium fluoride (2.14 g, 36.9 mmol). The reaction mixture was heated at 130° C. for 24 h. Reaction mixture was analyzed by GC-MS and 19F NMR. Data for 4,5-difluoro-6-phenylpicolinoyl fluoride, GC-MS: m/z=237, 189; 19F NMR (376 MHz, Toluene-d8) δ 17.03 (s), −124.14 (d, J=19.1 Hz), −140.76 (d, J=19.1 Hz). Reaction was allowed to cool to room temperature and triethylamine (1.1 mL, 7.7 mmol) and isopropanol (0.7 mL, 9.2 mmol) were added. After stirring for 1.5 h, the reaction mixture was diluted with water (100 mL) and transferred to a reparatory funnel. The reaction mixture was extracted with methyl tert-butyl ether (MTBE, 2×50 mL). The combined organic extracts were washed with water (3×50 mL) and saturated NaCl (50 mL) and concentrated under reduced pressure to provide a brown oil. The crude product oil was purified by silica gel flash chromatography (hexane/ethyl acetate gradient, 100% hexane→20% hexane/ethyl acetate) to provide 1.2 g (70% yield) of isopropyl 4,5-difluoro-6-phenylpicolinate as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.07-7.99 (m, 2H), 7.89 (dd, J=9.4, 5.3 Hz, 1H), 7.56-7.42 (m, 3H), 5.31 (hept, J=6.3 Hz, 1H), 1.43 (d, J=6.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 162.89 (d, J=3.4 Hz), 156.74 (dd, J=264.2, 12.5 Hz), 148.07 (dd, J=268.9, 10.8 Hz), 146.99 (dd, J=309.2, 10.8 Hz), 145.45 (s), 134.12-133.60 (m), 130.20 (s), 129.05 (d, J=5.9 Hz), 128.64 (s), 113.56 (d, J=16.0 Hz), 70.14 (s), 21.86 (s); 19F NMR (376 MHz, CDCl3) δ −125.22 (dd, J=17.7, 9.5 Hz), −144.74 (dd, J=17.7, 5.4 Hz); MS Calcd. for C15H13F2NO2: 277.09. Found: 277 (M+), 218, 191.

Aufarbeitung

  1. customReaction mixture
  2. customReaction
  3. temperatureto cool to room temperature
  4. customtransferred to a reparatory funnel
  5. extractionThe reaction mixture was extracted with methyl tert-butyl ether (MTBE, 2×50 mL)
  6. washThe combined organic extracts were washed with water (3×50 mL) and saturated NaCl (50 mL)
  7. concentrationconcentrated under reduced pressure
  8. customto provide a brown oil
  9. customThe crude product oil was purified by silica gel flash chromatography (hexane/ethyl acetate gradient, 100% hexane→20% hexane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-b7fc0b0e638541869737ee9ffc776fac
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08871943B2

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