[5-(2-Aminophenylethynyl)-2,4-dimethoxyphenyl]methanol → [5-(1H-indol-2-yl)-2,4-dimethoxyphenyl]methanol

HRID 347381Notes

Reaction equation

HRID 347381 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]#[C:9][C:10]1[C:11]([O:20][CH3:21])=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH2:16][OH:17])[CH:15]=1>C(#N)C.Cl[Pd]Cl>[NH:1]1[C:2]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:8]=[C:9]1[C:10]1[C:11]([O:20][CH3:21])=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH2:16][OH:17])[CH:15]=1

Participants

4

Reactant 1

HCID 11437548[5-(2-Aminophenylethynyl)-2,4-dimethoxyphenyl]methanol

Product 1

HCID 21082531[5-(1H-indol-2-yl)-2,4-dimethoxyphenyl]methanolYield 67.8%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of [5-(2-aminophenylethynyl)-2,4-dimethoxyphenyl]methanol (Ex-57B, 9.65 g, 34 mmol) in 1 L of acetonitrile, was added PdCl2 (0.6 g, 3.4 mmol). The mixture was heated to reflux for about 0.5 h and the reaction was complete as indicated by HPLC. The mixture was cooled to room temperature and filtered. The filtrate was treated with 20 g of 3-mercaptopropyl functional silica gel with stirring for 30 min and then filtered. The filtrate was concentrated and the residue was recrystallized from EtOAc/hexanes to give 6.25 g (67.8%) of [5-(1H-indol-2-yl)-2,4-dimethoxyphenyl]methanol as off-white solid. 1H-NMR (Acetone-d6) δ 10 50 (br, 1H), 7.84 (s, 1H), 7.48 (d, J=7 Hz, 1H), 7.37 (d, J=8 Hz, 1H),6.91–7.03 (m, 2H), 6.79 (d, J=2 Hz, 1H), 6.77 (s, 1H), 4.59 (s, 2H), 3.98 (s, 3H), 3.88 (s, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for about 0.5 h
  3. filtrationfiltered
  4. additionThe filtrate was treated with 20 g of 3-mercaptopropyl functional silica gel
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe residue was recrystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-a95a7a845db0482fbda4982ed7121cd0
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

Loading…