Diethyl Ether → HCID 25115597, Verbindung

HRID 1099415

Reaktionsgleichung

Reaktionsgleichung von HRID 1099415
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(NC(C)C)(C)C.[CH3:19][O:20][C:21]1[N:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1.C(OCC)C.FC(F)(F)S(O[C:40]1[CH:49]=[CH:48][CH:47]=[C:46]2[C:41]=1[CH2:42][C@H:43]([N:50]([CH2:58]C1C=CC=CC=1)[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:44][O:45]2)(=O)=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:58]([N:50]([CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C@H:43]1[CH2:42][C:41]2[C:46](=[CH:47][CH:48]=[CH:49][C:40]=2[C:26]2[CH:25]=[C:24]([O:27][CH3:28])[N:23]=[N:22][C:21]=2[O:20][CH3:19])[O:45][CH2:44]1)[C:8]1[CH:7]=[CH:6][CH:11]=[CH:10][CH:9]=1

Komponenten

12

Edukt 7

HCID 3283Diethyl EtherHCID 7912DiisopropylamineHCID 8058HexaneHCID 783483,6-DimethoxypyridazineHCID 516892Sodium BicarbonateHCID 25053925(3S)-3-(Dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonateHCID 178418339Butyllithium

Produkt 1

HCID 25115597HCID 25115597, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To tetrahydrofuran (2.0 mL) cooled to −20° C. a solution of n-butyllithium 2.5 M in hexane (0.644 mL, 1.61 mmol) was added via syringe. After 5 min diisopropylamine (0.227 mL, 1.61 mmol) was added and the reaction mixture was stirred for 15 min at that temperature and then cooled down to −78° C. A solution of 3,6-dimethoxypyridazine (0.098 g, 0.7 mmol) in tetrahydrofuran (2.0 mL) was added and the reaction mixture was stirred for 1 h at −78° C. Zinc chloride 1.0 M solution in diethylether (1.610 mL, 1.61 mmol) was added and the reaction mixture was allowed to warm up to ambient temperature. A solution of (3S)-3-(Dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonate (0.368 g, 0.77 mmol) in tetrahydrofuran (2.0 mL) and tetrakis(triphenylphosphine)palladium(0) (0.032 g, 0.03 mmol) were added and the reaction mixture was heated to reflux for 16 hours. The reaction mixture was diluted with ethyl acetate and added saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate, concentrated in vacuo and purified by column chromatography using a gradient of ethyl acetate in heptane yielding 0.235 g (72%) of the desired compound as a colorless oil; 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.36 (m, 8 H), 7.19-7.25 (m, 2 H), 7.15 (t, 1 H), 6.87 (dd, 1 H), 6.81 (s, 1 H), 6.71 (dd, 1 H), 4.34 (dd, 1 H), 4.14 (s, 3 H), 4.04-4.09 (m, 1 H), 4.03 (s, 3 H), 3.69 (s, 4 H), 3.23 (br. s., 1 H), 2.29-2.99 (m, 2 H); MS (APPI/APCI) m/z 468[M+H+].

Aufarbeitung

  1. additionwas added via syringe
  2. stirringthe reaction mixture was stirred for 1 h at −78° C
  3. temperatureto warm up to ambient temperature
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux for 16 hours
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-30fac3552b4a4881bb997150964ba5c6
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143408B2

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