Diisopropylamine → 2-Chloro-alpha-(3-methoxyphenyl)-3-pyridinemethanol

HRID 852088

Reaktionsgleichung

Reaktionsgleichung von HRID 852088
C([Li])CCC.C(NC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[CH:28](=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[Cl:21][C:22]1[C:27]([CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=2)[OH:37])=[CH:26][CH:25]=[CH:24][N:23]=1

Komponenten

10

Edukt 6

HCID 7912DiisopropylamineHCID 79772-ChloropyridineHCID 115693-MethoxybenzaldehydeHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Produkt 1

HCID 201457332-Chloro-alpha-(3-methoxyphenyl)-3-pyridinemethanolAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×HCID 8058HexaneLösungsmittel

Versuchsvorschrift

Combine 2.5 M n-butyl lithium in hexane (40 mL), diisopropyl amine (14 mL, 0.10 mol) and cold (−68° C.) tetrahydrofuran (250 mL) and stir for 20 minutes, to generate lithium diisopropylamide. Add 2-chloro-pyridine (9.5 mL, 0.10 mol) dissolved in tetrahydrofuran (10 mL) and stir for 45 minutes. Add m-anisaldehyde (13.6 g, 0.10 mol) in 10 mL tetrahydrofuran, stir for 45 minutes and let warm to room temperature over the weekend. Pour reaction mixture into water, add saturated ammonium chloride (50 mL), separate and dry. Extract with ether (twice), wash combined aqueous layers with saturated sodium chloride, dry, evaporate and purify by flash (silica) chromatography using a graded solvent mixture of dichloromethane to 10% ethyl acetate in dichloromethane to give the title compound as an oil (12.74 g, 51% Yield). NMR agrees with the final, desired compound.

Aufarbeitung

  1. additionPour
  2. customseparate
  3. customdry
  4. extractionExtract with ether (twice),
  5. washwash
  6. customdry
  7. customevaporate
  8. custompurify by flash (silica) chromatography
  9. additiona graded solvent mixture of dichloromethane to 10% ethyl acetate in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-0b4136e69fa14d5aabb9d73c5cf3a4d0
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07253165B2

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