Carbon Dioxide → (3-Chloropyrazin-2-yl)-quinolin-7-ylmethanol

HRID 244105

Reaktionsgleichung

Reaktionsgleichung von HRID 244105
CC1(C)CCCC(C)(C)N1.C(=O)=O.[Li]CCCC.[Cl:19][C:20]1[CH:25]=[N:24][CH:23]=[CH:22][N:21]=1.[N:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([CH:36]=[O:37])[CH:34]=2)[CH:29]=[CH:28][CH:27]=1.[Li]C1C(Cl)=NC=CN=1>C1COCC1.CC(C)=O>[Cl:19][C:20]1[C:25]([CH:36]([C:33]2[CH:34]=[C:35]3[C:30]([CH:29]=[CH:28][CH:27]=[N:26]3)=[CH:31][CH:32]=2)[OH:37])=[N:24][CH:23]=[CH:22][N:21]=1

Komponenten

9

Edukt 6

HCID 280Carbon Dioxide2×HCID 130352,2,6,6-TetramethylpiperidineHCID 73277ChloropyrazineHCID 47122557-QuinolinecarboxaldehydeHCID 178418339ButyllithiumHCID 178506780HCID 178506780, Verbindung

Produkt 1

HCID 57680924(3-Chloropyrazin-2-yl)-quinolin-7-ylmethanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 2,2,6,6-tetramethylpiperidine (0.64 mL, 0.54 g, 3.8 mmol) in dry THF (10 mL), cooled by CO2(s)/acetone, was added nBuLi (2.5 M in hexanes; 1.6 mL, 4.0 mmol). The cooling bath was replaced with an ice/water bath for 15 min, and then the solution was re-cooled to −78° C. After 10 min, 2-chloropyrazine (0.29 mL, 0.37 g, 3.2 mmol) was added. A solution of quinoline-7-carbaldehyde (500 mg, 3.18 mmol) in dry THF (5 mL), cooled by CO2(s)/acetone, was transferred into the lithiochloropyrazine solution by cannula 30 min later, and the mixture was stirred at −78° C. for 2.5 h and at 0° C. for 0.5 h. The reaction was quenched by adding aq. HCl (2 mL of a 2 M solution) followed by aq. NH4Cl solution. The mixture was extracted with EtOAc (4×30 mL), combined EtOAc extracts were washed with water and brine and dried over MgSO4. The crude material was chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 2:1 (1-21)→1:1 (22-32)→1:4 (33-62)→EtOAc (63-66)], yielding the title compound as an orange foam; 1H NMR (CDCl3, 400 MHz) δ 4.87 (d, J=7.6 Hz, 1H), 6.26 (d, J=7.6 Hz, 1H), 7.41 (dd, J=4.4, 8.4 Hz, 1H), 7.60 (dd, J=1.6, 8.4 Hz, 1H), 7.82 (d, J=8.4 Hz, 1H), 8.02 (d, J=0.8 Hz, 1H), 8.14 (dd, J=0.8, 8.4 Hz, 1H), 8.41 (d, J=2.4 Hz, 1H), 8.60 (d, J=2.4 Hz, 1H), 8.91 (dd, J=1.6, 4.4 Hz, 1H). MS (ES+): m/z 272.1/274.1 (100/38) [MH+].

Aufarbeitung

  1. waitAfter 10 min
  2. customThe reaction was quenched
  3. additionby adding aq. HCl (2 mL of a 2 M solution)
  4. extractionThe mixture was extracted with EtOAc (4×30 mL)
  5. washwere washed with water and brine
  6. dry with materialdried over MgSO4
  7. customThe crude material was chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 2:1 (1-21)→1:1 (22-32)→1:4 (33-62)→EtOAc (63-66)]

Quellen und Nachweise

ORD-Eintrag
ord-249be356720e42159188dc07db8865c8
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653268B2

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