Ethyl Acetate → 7-Chloro-8-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole

HRID 392085

반응식

HRID 392085 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:14](OCC)=O)[N:8]2[CH2:11][C:12]#[N:13])=[CH:4][C:3]=1[CH3:19].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Na].[K].C(OCC)(=O)C>CCOCC>[Cl:1][C:2]1[C:3]([CH3:19])=[CH:4][C:5]2[CH:6]=[C:7]3[CH2:14][NH:13][CH2:12][CH2:11][N:8]3[C:9]=2[CH:10]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 16211683Potassium alloy, nonbase, K,NaHCID 21226445Aluminium lithium hydride2회HCID 21868765Ethyl 6-chloro-1-(cyanomethyl)-5-methylindole-2-carboxylate

생성물 1

HCID 218687407-Chloro-8-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole수율 19%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

실험 절차

Ethyl 6chloro-1-(cyanomethyl)-5-methylindole-2-carboxylate (1.75 g, 6.3 mmol) was added portionwise over 2 min to a stirred solution of lithium aluminium hydride (0.61 g, 16 mmol) in ether (50 mL) at room temperature under Ar. The reaction was then heated to reflux and stirred for 70 h. The mixture was cooled to room temperature, a further portion of lithium aluminium hydride (0.61 g) was added and the reaction was heated to reflux and stirred for 18 h. The mixture was allowed to cool and then poured into aqueous potassium sodium tare solution (200 mL) and ethyl acetate (150 mL). The mixture was filtered through celite and the aqueous and organic layers were separated. The aqueous was extracted with ethyl acetate (2×100 mL) and the combined organic extracts were washed with brine (1×100 mL) dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol, (100:0)→(9:1)] to give the product as a yellow solid (027 g, 19%). IR νmax (Nujol)/cm−1 3351, 3190, 2922, 2731, 1734, 1647, 1615, 1562, 1543, 1457, 1416, 1378, 1350, 1316, 1304, 1261, 1246, 1223, 1182, 1157, 1134, 1116, 1028, 983, 972, 962, 902, 883, 835, 800, 782, 732, 700, 666, 632, 617, 558, 510 and 496; NMR δH (400 MHz; CDCl3) 7.35 (1H, s), 725 (1H, s), 6.06 (1H, m), 4.16 (2H, s), 3.91 (2H, t, J 5.5 Hz), 3.31 (2H, t, J 5.5 Hz), 2.42 (3H, s).

후처리

  1. temperatureThe reaction was then heated
  2. temperatureto reflux
  3. temperaturethe reaction was heated
  4. temperatureto reflux
  5. stirringstirred for 18 h
  6. temperatureto cool
  7. filtrationThe mixture was filtered through celite
  8. customthe aqueous and organic layers were separated
  9. extractionThe aqueous was extracted with ethyl acetate (2×100 mL)
  10. washthe combined organic extracts were washed with brine (1×100 mL)
  11. dry with materialdried (magnesium sulfate)
  12. filtrationfiltered
  13. customthe solvent removed under vacuum
  14. customto leave a crude oil
  15. customThe oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol, (100:0)→(9:1)]

출처 및 근거

ORD 기록
ord-3acc8bde85b64ee0a2eee9a32decf20c
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06800627B1

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