p-Toluenesulfonic acid → 2a-Methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one

HRID 2426163Notes

Reaction equation

HRID 2426163 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:12][C:13]([O:15]CC)=O)([CH3:11])[CH2:5][NH:6]2.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH3:11][C:4]12[CH2:5][NH:6][C:7]3[C:3]1=[C:2]([CH:10]=[CH:9][CH:8]=3)[NH:1][C:13](=[O:15])[CH2:12]2

Participants

3

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 86629731(+/-)-Ethyl (4-amino-3-methyl-2,3-dihydro-1H-indol-3-yl)acetate

Product 1

HCID 576637472a-Methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one

Procedure

A mixture of (±)-ethyl (4-amino-3-methyl-2,3-dihydro-1H-indol-3-yl)acetate from Step B (2.50 g, 10.7 mmol) and p-toluenesulfonic acid (2 mg, 0.01 mmol) was heated in xylenes (50 mL) at reflux for 13 h, then concentrated to dryness under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:N4OH—100:0:0 to 90:4.5:0.5, to give the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with hexane:i-PrOH:Et2NH—75:25:0.1. The first major peak to elute was 2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer A, the title compound, and the second major peak to elute was 2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer B. MS: m/z=189 (M+1).

Workup

  1. temperatureat reflux for 13 h
  2. concentrationconcentrated to dryness under reduced pressure
  3. customThe crude product was purified by silica gel chromatography
  4. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-84132156976c4a9298ba057a2b36d271
Source dataset
uspto-grants-2011_06
Patent number
US07968540B2

Reaction notes

Loading…