Dimethyl Sulfide → 3-((2R,5S)-3,6-Diethoxy-5-isopropyl-2,5-dihydro-pyrazin-2-yl)-cycloheptanone

HRID 77329

Reaktionsgleichung

Reaktionsgleichung von HRID 77329
[CH2:1]([O:3][C:4]1[C@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=[C:7]([O:10][CH2:11][CH3:12])[CH2:8][N:9]=1)[CH3:2].C([Li])CCC.CSC.[C:24]1(=[O:31])[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]=[CH:25]1.N1C=CN=CC1>O1CCCC1>[CH2:11]([O:10][C:7]1[C@@H:8]([CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30][C:24](=[O:31])[CH2:25]2)[N:9]=[C:4]([O:3][CH2:1][CH3:2])[C@H:5]([CH:13]([CH3:14])[CH3:15])[N:6]=1)[CH3:12]

Komponenten

7

Edukt 5

HCID 1068Dimethyl SulfideHCID 707232-Cyclohepten-1-oneHCID 426210DihydropyrazineHCID 11020211(S)-2,5-Dihydro-3,6-diethoxy-2-isopropylpyrazineHCID 178418339Butyllithium

Produkt 1

HCID 671552883-((2R,5S)-3,6-Diethoxy-5-isopropyl-2,5-dihydro-pyrazin-2-yl)-cycloheptanoneAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of (S)-3,6-diethoxy-2-isopropyl-2,5-dihydro-pyrazine (6.0 g, 28.3 mmol) in tetrahydrofuran (58 mL) is cooled to −78° C. n-butyllithium (1.6 M in hexane, 21.4 mL, 34.2 mmol) is added slowly via syringe, and the reaction is allowed to stir at −78° C. for 30 minutes. The reaction mixture is then transferred via canula to a solution of CuBr-Me2S (3.35 g, 16.3 mmol) in tetrahydrofuran:dimethylsulfide (90 mL, [2:1]) at −50° C. The reaction is warmed to −30° C. and stirred further for 30 minutes. The reaction is then cooled to −78° C. and cyclohept-2-eneone (5.23 mL, 46.9 mmol) is added dropwise over 10 minutes. The reaction is maintained at −78° C. until the disappearance of the dihydropyrazine is confirmed by TLC and quenched by the addition of a saturated aqueous solution of ammonium chloride at −78° C. The reaction is allowed to warm to ambient temperature, diluted with water, and extracted with diethyl ether. The organic extracts were washed with ammonium chloride, dilute ammonium hydroxide, water and brine, dried over magnesium sulfate, and concentrated in vacuo. The residue is purified by column chromatography eluting with a gradient of hexane in ether (20-25%) to afford the title compound (6.52 g, 72% yield), slightly contaminated with cyclohept-2-enone. LCMS (m/z): 323.13 (M+1).

Aufarbeitung

  1. additionis added slowly via syringe
  2. customat −50° C
  3. temperatureThe reaction is warmed to −30° C.
  4. stirringstirred further for 30 minutes
  5. temperatureThe reaction is then cooled to −78° C.
  6. customquenched by the addition of a saturated aqueous solution of ammonium chloride at −78° C
  7. temperatureto warm to ambient temperature
  8. additiondiluted with water
  9. extractionextracted with diethyl ether
  10. washThe organic extracts were washed with ammonium chloride, dilute ammonium hydroxide, water and brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe residue is purified by column chromatography
  14. washeluting with a gradient of hexane in ether (20-25%)

Quellen und Nachweise

ORD-Eintrag
ord-162576ab5c634c32b0476a855e6b54f4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841291B2

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