Reaction #11514

Reaction equation

potassium carbonate

para-Tolylphosphine

2-bromopyridine

Trimethylborate

THF

2-bromoindole

THF

→

Methyl 1-cyclopentyl-3-methyl-2-(2-pyridyl)indole-5-carboxylate

Solvents

water

TBME

MeOH

Conditions

Workup

1. 1
   workup.STIRRINGthe solution stirred at −78° C. for 40 min
2. 2
   workup.WAITat 0° C. for 1 h
3. 3
   Temperatureto warm up to room temperature
4. 4
   Otherthe solution was degassed
5. 5
   Otherby bubbling argon through for 30 min
6. 6
   Temperaturethe mixture was refluxed overnight under an argon atmosphere
7. 7
   TemperatureAfter cooling to RT
8. 8
   Otherthe organic phase was separated
9. 9
   Extractionthe aqueous phase extracted with additional TBME (2×25 mL)
10. 10
    WashThe combined organic layers were washed with brine
11. 11
    Dryingdried (Na2SO4)
12. 12
    Concentrationconcentrated
13. 13
    Otherto give a residue that
14. 14
    Otherwas purified by flash chromatography on silica gel using 5–10% EtOAc in hexane as eluent

Procedure

The 2-bromoindole from above (1.53 g, 4.55 mmol, 1.0 equiv.) was dissolved in anhydrous THF (20 mL) and the solution was cooled to −78° C. under an argon atmosphere. N-BuLi (solution in hexane, 4.78 mmol, 1.05 equiv.) was added dropwise and the mixture was stirred 30 min in the cold. Trimethylborate (0.62 mL, 5.46 mmol, 1.2 equiv.) was added dropwise and the solution stirred at −78° C. for 40 min and then at 0° C. for 1 h. Finally the reaction mixture was allowed to warm up to room temperature and additional THF (20 mL) was added. para-Tolylphosphine (0.083 g, 0.27 mmol, 0.06 equiv.) and 2-bromopyridine (0.86 g, 5.46 mmol, 1.2 equiv.) were then added and the solution was degassed by bubbling argon through for 30 min. Palladium acetate (10 mg, 0.046 mmol, 0.01 equiv.), anhydrous potassium carbonate (1.26 g, 9.1 mmol, 2 equiv.) and MeOH (20 mL) were added and the mixture was refluxed overnight under an argon atmosphere. After cooling to RT, TBME (12 mL) and water (12 mL) were added, the organic phase was separated and the aqueous phase extracted with additional TBME (2×25 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to give a residue that was purified by flash chromatography on silica gel using 5–10% EtOAc in hexane as eluent: 1.21 g (79%).

Source