Cesium carbonate → Ethyl 5-[(phenylmethyl)oxy]-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

HRID 913385Notes

Reaction equation

HRID 913385 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].FC(F)(F)S(O[CH2:35][C:36]([F:39])([F:38])[F:37])(=O)=O>CC#N.CN(C=O)C>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH2:35][C:36]([F:39])([F:38])[F:37])[C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 95721Ethyl 5-(phenylmethoxy)-1H-indole-2-carboxylate

Product 1

HCID 57800458Ethyl 5-[(phenylmethyl)oxy]-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Procedure

To a solution of ethyl 5-[(phenylmethyl)oxy]-1H-indole-2-carboxylate (0.3 g, 1 mmol) in 3:2 MeCN/DMF (5 mL) was added Cs2CO3 (0.36 g, 1.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.26 g, 1.1 mmol). The mixture was stirred at rt, under N2, for 4 h. Additional Cs2CO3 (0.033 g, 0.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.023 g, 0.1 mmol) were added and stirring was continued at rt for 15 h. The mixture was partitioned between Et2O and 0.05N HCl. The organic phase was washed with 0.05N HCl and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient) to afford the title compound (0.23 g, 61% yield): 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J=7.1 Hz, 2H), 7.38 (t, J=7.1 Hz, 2H), 7.34-7.29 (m, 3H), 7.16-7.13 (m, 2H), 5.28 (q, J=8.5 Hz, 2H), 5.10 (s, 2H), 4.37 (q, J=7.1 Hz, 2H), 1.39 (t, J=7.1 Hz, 3H).

Workup

  1. stirringstirring
  2. waitwas continued at rt for 15 h
  3. customThe mixture was partitioned between Et2O and 0.05N HCl
  4. washThe organic phase was washed with 0.05N HCl
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-fbffe142ccf0478c84f1ff5056415eff
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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