6-(Bromomethyl)quinoline → 6-{[(2S,5R)-3,6-dimethoxy-5-(propan-2-yl)-2,5-dihydropyrazin-2-yl]methyl}quinoline

HRID 74815Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 74815
[CH3:1][O:2][C:3]1[C@@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])CCC.Br[CH2:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][CH:25]=[CH:24]2>O1CCCC1>[CH3:10][O:9][C:6]1[C@H:7]([CH2:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[N:27]=[CH:26][CH:25]=[CH:24]3)[N:8]=[C:3]([O:2][CH3:1])[C@@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=1

Komponenten

5

Edukt 3

HCID 2243966-(Bromomethyl)quinolineHCID 736066(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazineHCID 178418339Butyllithium

Produkt 1

HCID 866857696-{[(2S,5R)-3,6-dimethoxy-5-(propan-2-yl)-2,5-dihydropyrazin-2-yl]methyl}quinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a cooled solution (−70° C.) of (2R)-3,6-dimethoxy-2-(propan-2-yl)-2,5-dihydropyrazine (25.8 g, 140 mmol, 2 eq.) in tetrahydrofuran (200 mL) was added dropwise n-butyllithium (2.5 M, 64.4 mL, 161 mmol 2.3 eq.) and then stirred for 30 minutes. A solution of #210 (15.4 g, 70 mmol, 1 eq.) in tetrahydrofuran (150 mL) was added dropwise at −65° C. and then the solution was stirred for 2 hours at this temperature. The reaction was quenched by saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (100 mL). The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica column chromatography (Gradient: 10 to 16% ethyl acetate in petroleum ether) to afford #211 (7.3 g, 32%, over two steps) as yellow solid. LC-MS (Protocol Z): m/z 326.2 [M+H+], retention time=0.88 minutes.

Aufarbeitung

  1. stirringthe solution was stirred for 2 hours at this temperature
  2. customThe reaction was quenched by saturated aqueous ammonium chloride (100 mL)
  3. extractionextracted with ethyl acetate (100 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica column chromatography (Gradient: 10 to 16% ethyl acetate in petroleum ether)
  7. customto afford #211 (7.3 g, 32%, over two steps) as yellow solid

Quellen und Nachweise

ORD-Eintrag
ord-0890b0a8f5d041eebfbaef034b9c7509
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828401B2

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