1-Acetyl-4-benzoylpiperidine → 1-(4-(Hydroxy(phenyl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)methyl)piperidin-1-yl)ethanone

HRID 627564

Reaktionsgleichung

Reaktionsgleichung von HRID 627564
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[C:5]2[C:22]([F:25])([F:24])[F:23].C([Mg]Cl)(C)C.[C:31]([CH:39]1[CH2:44][CH2:43][N:42]([C:45](=[O:47])[CH3:46])[CH2:41][CH2:40]1)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[OH:38][C:31]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:13])([F:15])[F:14])[C:6]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[C:5]2[C:22]([F:23])([F:24])[F:25])[CH:39]1[CH2:40][CH2:41][N:42]([C:45](=[O:47])[CH3:46])[CH2:43][CH2:44]1

Komponenten

5

Edukt 3

HCID 27407141-Acetyl-4-benzoylpiperidine2×HCID 86716066HCID 86716066, Verbindung2×HCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 734428551-(4-(Hydroxy(phenyl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)methyl)piperidin-1-yl)ethanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A ˜−70° C. solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (754 mg, 1.61 mmol, Intermediate 8, step d) in THF (1.4 mL) was treated with iPrMgCl (0.784 mL, 2.06 M in THF, 1.61 mmol) dropwise via syringe under argon over the course of 3 min to provide a light amber solution. After 9 min, the opaque yellow slurry was removed from the cold bath and stirred under ambient conditions for 4 min. A solution of 1-(4-benzoylpiperidin-1-yl)ethanone (442 mg, 1.91 mmol, Intermediate 27) in THF (0.3 mL) was added to the olive drab slurry rapidly dropwise over ˜15 sec, and the homogeneous brown solution was stirred at room temperature overnight. The light amber solution was then quenched with 5 M NH4Cl (1 mL) and extracted with 2-methoxy-2-methylpropane (1×10 mL, 1×2 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was flash chromatographed using 50% acetone/heptane (isocratic elution), and impure fractions were additionally flash chromatographed using 90% EtOAc/heptanes (isocratic elution) to afford the title compound as an off-white foam. 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J=10.11 Hz, 1H), 8.24 (dd, J=5.56, 9.09 Hz, 1H), 7.94 (t, J=8.84 Hz, 1H), 7.54 (t, J=7.33 Hz, 2H), 7.41-7.51 (m, 3H), 7.33-7.41 (m, 2H), 7.28 (br. s., 3H), 4.71 (d, J=7.58 Hz, 1H), 3.86 (br. s., 1H), 3.00-3.21 (m, 1H), 2.74-2.89 (m, 1H), 2.52-2.69 (m, 1H), 2.44-2.52 (m, 1H; D2O-exch), 2.05 (d, J=2.02 Hz, 3H), 1.69-1.84 (m, 1H), 1.31-1.55 (m, 3H); MS m/e 573.0 [M+H]+.

Aufarbeitung

  1. customto provide a light amber solution
  2. customthe opaque yellow slurry was removed from the cold bath
  3. stirringthe homogeneous brown solution was stirred at room temperature overnight
  4. customThe light amber solution was then quenched with 5 M NH4Cl (1 mL)
  5. extractionextracted with 2-methoxy-2-methylpropane (1×10 mL, 1×2 mL)
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed
  10. customchromatographed

Quellen und Nachweise

ORD-Eintrag
ord-91039dd44ebb43ef9a86a8c2b5343f07
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309222B2

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