반응 #164511

반응 방정식

dimethylsulfide

dihydropyrazine

(S)-3,6-diethoxy-2-isopropyl-2,5-dihydro-pyrazine

n-butyllithium

cyclohept-2-eneone

→

title compound

수율 72.0%

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

수율 72.0%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONis added slowly via syringe
2. 2
   기타at −50° C
3. 3
   온도The reaction is warmed to −30° C.
4. 4
   workup.STIRRINGstirred further for 30 minutes
5. 5
   온도The reaction is then cooled to −78° C.
6. 6
   기타quenched by the addition of a saturated aqueous solution of ammonium chloride at −78° C
7. 7
   온도to warm to ambient temperature
8. 8
   workup.ADDITIONdiluted with water
9. 9
   추출extracted with diethyl ether
10. 10
    세척The organic extracts were washed with ammonium chloride, dilute ammonium hydroxide, water and brine
11. 11
    건조dried over magnesium sulfate
12. 12
    농축concentrated in vacuo
13. 13
    기타The residue is purified by column chromatography
14. 14
    세척eluting with a gradient of hexane in ether (20-25%)

실험 절차

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).

출처