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

Temperatur

-78 °C

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%).

1. stirringthe solution stirred at −78° C. for 40 min
2. waitat 0° C. for 1 h
3. temperatureto warm up to room temperature
4. customthe solution was degassed
5. customby bubbling argon through for 30 min
6. temperaturethe mixture was refluxed overnight under an argon atmosphere
7. temperatureAfter cooling to RT
8. customthe organic phase was separated
9. extractionthe aqueous phase extracted with additional TBME (2×25 mL)
10. washThe combined organic layers were washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. customto give a residue that
14. customwas purified by flash chromatography on silica gel using 5-10% EtOAc in hexane as eluent

ORD-Eintrag

ord-1dc8eae914574be3852fe8e62573e3c4

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07838537B2