Cesium carbonate → (+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)benzofuran-6-carbonitrile

HRID 2174091Notes

Reaction equation

HRID 2174091 reaction equation
[C:1]([C:3]1[CH:32]=[CH:31][C:6]2[CH:7]=[C:8]([CH:10]([OH:30])[C:11]3[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]4[C:12]=3[CH:13]=[CH:14][N:15]4C(OC(C)(C)C)=O)[O:9][C:5]=2[CH:4]=1)#[N:2].C([O-])([O-])=O.[Cs+].[Cs+]>CO>[OH:30][CH:10]([C:11]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]2[C:12]=1[CH:13]=[CH:14][NH:15]2)[C:8]1[O:9][C:5]2[CH:4]=[C:3]([C:1]#[N:2])[CH:32]=[CH:31][C:6]=2[CH:7]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 86701726tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701727(+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)benzofuran-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (28 mg, 0.065 mmol) in MeOH (0.65 mL) at room temperature, Cs2CO3 (105 mg, 0.324 mmol) was added and the reaction was stirred at 60° C. After 30 minutes the reaction was cooled to room temperature and quenched with sat. aq. NH4Cl. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic phases were dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-80% EtOAc:Heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.86 (br. s., 1H) 8.03 (s, 1H) 7.66-7.78 (m, 1H) 7.58 (dd, J=8.08, 1.39 Hz, 1H) 7.18 (t, J=2.78 Hz, 1H) 6.83 (t, J=1.07 Hz, 1H) 6.76 (s, 1H) 6.41-6.55 (m, 2H) 6.03 (d, J=4.93 Hz, 1H) 3.80 (s, 3H) 2.39-2.47 (m, 3H). HRMS calcd. for C20H16N2O3 (M+H)+ 333.1234. found 333.1237.

Workup

  1. temperatureAfter 30 minutes the reaction was cooled to room temperature
  2. customquenched with sat. aq. NH4Cl
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (0-80% EtOAc:Heptanes)

Sources & evidence

ORD record
ord-8d7cba30da1440208164617366a48b80
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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