반응 #11514

반응 방정식

potassium carbonate

para-Tolylphosphine

2-bromopyridine

Trimethylborate

THF

2-bromoindole

THF

→

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

용매

water

TBME

MeOH

반응 조건

후처리

1. 1
   workup.STIRRINGthe solution stirred at −78° C. for 40 min
2. 2
   workup.WAITat 0° C. for 1 h
3. 3
   온도to warm up to room temperature
4. 4
   기타the solution was degassed
5. 5
   기타by bubbling argon through for 30 min
6. 6
   온도the mixture was refluxed overnight under an argon atmosphere
7. 7
   온도After cooling to RT
8. 8
   기타the organic phase was separated
9. 9
   추출the aqueous phase extracted with additional TBME (2×25 mL)
10. 10
    세척The combined organic layers were washed with brine
11. 11
    건조dried (Na2SO4)
12. 12
    농축concentrated
13. 13
    기타to give a residue that
14. 14
    기타was purified by flash chromatography on silica gel using 5–10% EtOAc in hexane as eluent

실험 절차

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%).

출처