4-(3-Bromo-5-chlorophenyl)morpholine → HCID 59631266, Verbindung

HRID 1431760Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1431760
Br[C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([CH:33]=[O:34])=[C:21]([CH3:32])[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:23]2)=[CH:18][CH:17]=1>C1COCC1>[Cl:8][C:6]1[CH:7]=[C:2]([CH:33]([C:20]2[C:19]3[C:24](=[CH:25][C:16]([F:15])=[CH:17][CH:18]=3)[N:23]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[C:21]=2[CH3:32])[OH:34])[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=1

Komponenten

4

Edukt 2

HCID 532170884-(3-Bromo-5-chlorophenyl)morpholineHCID 59631569HCID 59631569, Verbindung

Produkt 1

HCID 59631266HCID 59631266, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

An oven-dried conical flask was charged with 4-(3-bromo-5-chlorophenyl)-morpholine (0.384 g, 1.390 mmol) and 1.0 mL THF. While this solution was stirring at −78° C. under nitrogen, 2.5M butyllithium hexanes (0.556 mL, 1.390 mmol) was added via syringe. This solution was stirred at −78° C. for 30 minutes. After this time a solution of 7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline-4-carbaldehyde (0.074 g, 0.278 mmol) in 2.0 mL THF was added, and the reaction continued at −78° C. for 45 minutes. Upon completion, the reaction was quenched with satd aqueous ammonium chloride and concd. The resulting material was partitioned between EtOAc and water, and the organic phase was dried over magnesium sulfate and concd. The afforded crude product was purified by column chromatography (silica; 0-50% EtOAc in hexanes) to yield (3-chloro-5-(4-morpholinyl)phenyl)(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)methanol as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, d), 8.35 (1H, m), 8.01 (1H, t), 7.83 (1H, s), 7.71 (1H, d), 7.51 (1H, m), 7.42 (1H, m), 6.97 (1H, s), 6.83 (1H, s), 6.64 (1H, d, J=4.5 Hz), 6.55 (1H, d), 6.51 (1H, s), 3.69 (4H, t, J=4.8 Hz), 3.08 (4H, d, J=3.9 Hz), 2.46 (3H, s). Mass Spectrum (ESI) m/e=464.0 (M+1).

Aufarbeitung

  1. stirringThis solution was stirred at −78° C. for 30 minutes
  2. customUpon completion, the reaction was quenched with satd aqueous ammonium chloride and concd
  3. customThe resulting material was partitioned between EtOAc and water
  4. dry with materialthe organic phase was dried over magnesium sulfate and concd
  5. customThe afforded crude product
  6. customwas purified by column chromatography (silica; 0-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-ae3f3798d0184943b8a40231a990dbe7
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940724B2

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