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

HRID 857452

反応式

HRID 857452 の反応式
[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-].C(C(C(C([O-])=O)O)O)([O-])=O.[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

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 9855836Potassium sodium tartarateHCID 21226445Aluminium lithium hydride2 回HCID 21868765Ethyl 6-chloro-1-(cyanomethyl)-5-methylindole-2-carboxylate

生成物 1

HCID 218687407-Chloro-8-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole収率 19.4%

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

実験手順

Ethyl 6-chloro-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 temeperature, 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 tartrate 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 (0.27 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), 7.25 (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).

後処理

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

出典と根拠

ORDレコード
ord-bcc1a53e9d3f4227906e8914d6ccd374
出典データセット
uspto-grants-2006_12
特許番号
US07145009B2

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