Toluene → HCID 178469168, compound

HRID 1912631Notes

Reaction equation

HRID 1912631 reaction equation
[NH2:1][C:2]1[N:3]([CH3:15])[C:4]2[C:9]([C:10]=1[C:11]([O:13]C)=O)=[CH:8][CH:7]=[CH:6][CH:5]=2.CC1C=CC(S(O)(=O)=[O:24])=CC=1.[O-:27][CH2:28][CH3:29].[Na+].[C:31]1([CH3:37])[CH:36]=[CH:35]C=CC=1>>[OH:13][C:11]1[C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([CH3:15])[C:2]=2[N:1]=[C:31]([CH3:37])[C:36]=1[C:35]([O:27][CH2:28][CH3:29])=[O:24]

Participants

5

Reactant 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 2723922Sodium ethoxideHCID 15154327HCID 15154327, compound

Product 1

HCID 178469168HCID 178469168, compoundYield 37.1%

Conditions

Temperature
0 °C

Procedure

A solution methyl 2-amino-1-methyl-1H-indole-3-carboxylate (426 mg, 2.1 mmol) in toluene (9039 μl) was treated with pTsOH (39.7 mg, 0.209 mmol) and heated to reflux with a Dean-Stark trap. After 4 h, the reaction mixture was cooled to 0° C. and treated with sodium ethoxide (1012 μl, 2.71 mmol) and subsequently heated to reflux (135° C. bath temp). After 18 h, the reaction mixture was cooled to ambient temperature and partitioned between EtOAc and 1M HCl. The organics were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-35% EtOAc-hexanes) to afford ethyl 4-hydroxy-2,9-dimethyl-9H-pyrido[2,3-b]indole-3-carboxylate (220 mg, 0.774 mmol, 37.1% yield) as a yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ=12.94 (s, 1 H), 8.27 (d, J=7.8 Hz, 1 H), 7.53-7.46 (m, 1 H), 7.45 (s, 1 H), 7.35 (s, 1 H), 4.51 (d, J=7.0 Hz, 2 H), 3.95 (s, 3 H), 2.93 (s, 3 H), 1.50 (s, 3 H); LCMS (m/z) ES+=285 (M+1).

Workup

  1. temperatureheated
  2. temperatureto reflux with a Dean-Stark trap
  3. temperaturesubsequently heated
  4. temperatureto reflux (135° C. bath temp)
  5. waitAfter 18 h
  6. temperaturethe reaction mixture was cooled to ambient temperature
  7. custompartitioned between EtOAc and 1M HCl
  8. washThe organics were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by ISCO (0-35% EtOAc-hexanes)

Sources & evidence

ORD record
ord-d24c931c96ef443ab9907b77d1534cf5
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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