p-Toluenesulfonic acid monohydrate → HCID 86642128, compound

HRID 641443Notes

Reaction equation

HRID 641443 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:18][C:19]([O:21]CC)=O)([CH3:17])[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>[CH3:17][C:4]12[CH2:5][N:6]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]3[C:3]1=[C:2]([CH:10]=[CH:9][CH:8]=3)[NH:1][C:19](=[O:21])[CH2:18]2

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 66636723HCID 66636723, compound

Product 1

HCID 86642128HCID 86642128, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of diethyl 2,2′-(4-amino-3-methyl-2,3-dihydro-1H-indole-1,3-diyl)diacetate from Step D (410 mg, 1.28 mmol) in toluene (100 mL) was added p-toluenesulfonic acid monohydrate (10 mg, 0.052 mmol) and the mixture was heated at reflux. After 20 min, the reaction was allowed to cool to ambient temperature and the mixture was partitioned between EtOAc (300 mL) and aqueous NaHCO3 (50 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:EtOAc—100:0 to 0:100, to give the racemic product. The enantiomers were resolved by HPLC, utilizing a Chiralpak AS column and eluting with hexane:EtOH 40:60. The first major peak to elute was ethyl (2a-methyl-4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer A, the title compound, and the second major peak to elute was ethyl (2a-methyl-4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer B. MS: m/z=275 (M+1).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux
  3. customthe mixture was partitioned between EtOAc (300 mL) and aqueous NaHCO3 (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2
  10. customEtOAc—100:0 to 0:100, to give the racemic product
  11. washeluting with hexane:EtOH 40:60
  12. washThe first major peak to elute
  13. washthe title compound, and the second major peak to elute

Sources & evidence

ORD record
ord-594ed090026145d08057700a6d44fe62
Source dataset
uspto-grants-2010_04
Patent number
US07696192B2

Reaction notes

Loading…