Ethyl Acetate → 7-Bromo-1,2,3,4-tetrahydropyrazino[1,2-a]indole

HRID 392081Notes

Reaction equation

HRID 392081 reaction equation
[Br: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][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+].C(OCC)(=O)C>CCOCC>[Br:1][C:2]1[CH:3]=[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

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9855836Potassium sodium tartarateHCID 21226445Aluminium lithium hydrideHCID 21868726Ethyl 6-bromo-1-cyanomethylindole-2-carboxylate

Product 1

HCID 218687617-Bromo-1,2,3,4-tetrahydropyrazino[1,2-a]indoleYield 44%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Ethyl 6-bromo-1-cyanomethylindole-2-carboxylate (3.1 g, 10 mmol) was added portionwise over 2-3 min to a stirred suspension of lithium aluminium hydride (0.95 g, mmol) in ether (100 mL) at room temperature under Ar. The reaction was then heated to reflux and stirred for 18 h. After allowing to cool to room temperature the mixture was poured slowly into stirred saturated aqueous sodium potassium tartrate solution (300 mL). The mixture was stirred for 10 min and ethyl acetate (200 mL) was added. The mixture was then filtered through celite and extracted with ethyl acetate (2×150 mL). The combined organic extracts were washed with brine (150 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; methanol-ethyl acetate-ammonium hydroxide (1:9:0)→(9:90:1)] to give the product as a yellow oil (1.1 g, 44%). IR νmax (Nujol)/cm−1 3310, 2925, 2855, 2725, 1886, 1666, 1604, 1563, 1535, 1458, 1411, 1378, 1366, 1340, 1321, 1301, 1278, 1242, 1217, 1201, 1169, 1139, 1128, 1114, 1048, 1000, 945, 924, 876, 844, 835, 812, 792, 751, 730, 699, 648, 619, 590, 562, 523 and 490. NMR δH (400 MHz; CDCl3) 7.42 (1H, m), 7.39 (1H, d, J 8.7 Hz), 7.19 (1H, dd, J 8.7 Hz, 2Hz), 6.17 (1H, m), 4.20 (2H, d, J 0.8 Hz), 3.97 (2H, t, J 5.8 Hz), 3.35 (2H, t, J 5.8 Hz), 1.63 (1H, br. s).

Workup

  1. temperatureThe reaction was then heated
  2. temperatureto reflux
  3. additionwas poured slowly
  4. stirringThe mixture was stirred for 10 min
  5. filtrationThe mixture was then filtered through celite
  6. extractionextracted with ethyl acetate (2×150 mL)
  7. washThe combined organic extracts were washed with brine (150 mL)
  8. dry with materialdried (magnesium sulfate)
  9. filtrationfiltered
  10. customthe solvent removed under vacuum
  11. customto leave a crude oil
  12. customThe oil was purified by flash column chromatography [SiO2; methanol-ethyl acetate-ammonium hydroxide (1:9:0)→(9:90:1)]

Sources & evidence

ORD record
ord-2687875c7e384fedb11f4bca01d4c8b3
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Reaction notes

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