Cesium carbonate → tert-Butyl 5-ethenyl-1H-indole-1-carboxylate

HRID 587227Notes

Reaction equation

HRID 587227 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)=[CH2:2].BrC1[CH:14]=[C:15]2[C:19](=CC=1)NC=[CH:16]2.C([B-](F)(F)F)=C.[K+].[C:29]([O-])([O-:31])=[O:30].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O.Cl[Pd]Cl>[C:15]([O:31][C:29]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([CH:1]=[CH2:2])=[CH:11][CH:10]=2)[CH:6]=[CH:7]1)=[O:30])([CH3:19])([CH3:16])[CH3:14]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 249055-BromoindoleHCID 126103725-Ethenyl-1H-indoleHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 66890900tert-Butyl 5-ethenyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 21881883Oxolane--water (1/1)Solvent

Procedure

5-Vinyl-1H-indole (BI18): A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs2CO3 (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl2 (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through Celite® bed and washed with EtOAc. The filtrate was again extracted with EtOAc, and the combined organic layer washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): 1H NMR (400 MHz, CDCl3) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M−H]−).

Workup

  1. customwas degassed with argon for 20 min
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 16 h
  4. filtrationfiltered through Celite® bed
  5. washwashed with EtOAc
  6. extractionThe filtrate was again extracted with EtOAc
  7. washthe combined organic layer washed with water and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customto afford the crude compound
  11. customThe crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-77f5c71d889b4ce184cff437d6fc7c7e
Source dataset
uspto-grants-2016_01
Patent number
US09226500B2

Reaction notes

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