p-Toluenesulfonic acid monohydrate → Ethyl(4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2h)-yl)acetate

HRID 641393Notes

Reaction equation

HRID 641393 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([CH2:17][C:18]([O:20]C)=O)[CH2:5][N:6]2[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:20]=[C:18]1[CH2:17][CH:4]2[CH2:5][N:6]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]3[C:3]2=[C:2]([CH:10]=[CH:9][CH:8]=3)[NH:1]1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 59257815HCID 59257815, compound

Product 1

HCID 59257825Ethyl(4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2h)-yl)acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (±)-ethyl methyl 2,2′-(4-amino-2,3-dihydro-1H-indole-1,3-diyl)diacetate from Step D (490 mg, 1.70 mmol) in toluene (35 mL) was added p-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) and the mixture was heated at reflux for 48 h. The mixture was cooled to ambient temperature and was partitioned between saturated aqueous NaHCO3 (5 mL) and EtOAc (40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CHCl3:EtOAc—90:10 to 40:60, to give the racemic product. The enantiomers were resolved by HPLC, utilizing a Chiralpak AS column and eluting with MeOH. The first major peak to elute was ethyl (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer A, and the second major peak to elute was ethyl (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2B)-yl)acetate, enantiomer B, the title compound. MS: m/z=261 (M+1).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 48 h
  3. customwas partitioned between saturated aqueous NaHCO3 (5 mL) and EtOAc (40 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of CHCl3
  9. customEtOAc—90:10 to 40:60, to give the racemic product
  10. washeluting with MeOH
  11. washThe first major peak to elute
  12. washthe second major peak to elute

Sources & evidence

ORD record
ord-f54152dc6c36432995669fefe9f49db8
Source dataset
uspto-grants-2010_04
Patent number
US07696192B2

Reaction notes

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