Trifluoroacetic acid → Ethyl cis-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylate

HRID 1748258Notes

Reaction equation

HRID 1748258 reaction equation
C(O[C:6]([NH:8][CH:9]([CH3:31])[CH:10]([N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:19]=2)[CH:14]=[C:13]1C(OCC)=O)[CH3:11])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C(O)C>[CH3:31][C@H:9]1[C@H:10]([CH3:11])[N:12]2[C:20]3[CH:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]2[C:6](=[O:7])[NH:8]1.[CH3:31][C@H:9]1[C@@H:10]([CH3:11])[N:12]2[C:20]3[CH:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]2[C:6](=[O:7])[NH:8]1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 67236196diethyl 1-[3-[(tert-butoxycarbonyl)amino]butan-2-yl]-1H-indole-2,6-dicarboxylate

Product 2

HCID 67235475Ethyl cis-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylateYield 45%HCID 86682387Ethyl trans-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylateYield 20%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the crude diethyl 1-{3-[(tert-butoxycarbonyl)amino]butan-2-yl}-1H-indole-2,6-dicarboxylate from the preceding reaction in CH2Cl2 (10 mL) is added TFA (10 mL). The mixture is stirred for 1 h at room temperature. The solvent is removed and the residue is dried in vacuo for 1 h. To a solution of the residue in ethanol (100 mL) is added K2CO3 (6.2 g, 44.8 mmol). The reaction mixture is refluxed for 1 h. After cooling to room temperature, the solvent is removed under vacuum and the residue is partitioned between EtOAc and water. The organic layer is separated, washed with brine, dried (MgSO4) and concentrated to afford the crude compound which is purified by flash column chromatography using EtOAc in heptane to afford ethyl trans-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-α]indole-7-carboxylate (870 mg, 20% for 2 steps) and ethyl cis-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylate (1.9 g, 45% for 2 steps).

Workup

  1. customThe solvent is removed
  2. customthe residue is dried in vacuo for 1 h
  3. temperatureThe reaction mixture is refluxed for 1 h
  4. temperatureAfter cooling to room temperature
  5. customthe solvent is removed under vacuum
  6. customthe residue is partitioned between EtOAc and water
  7. customThe organic layer is separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customto afford the crude compound which
  12. customis purified by flash column chromatography

Sources & evidence

ORD record
ord-6c6bbd408ba1467db6c32d2c824984c4
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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