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

HRID 1748258노트

반응식

HRID 1748258 반응식
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

참가 물질

7

반응물 3

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

생성물 2

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6c6bbd408ba1467db6c32d2c824984c4
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150577B2

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