Reaction #2487455

Reaction equation

5-methoxy-2-phenyl-1H-indole

sodium hydride

ammonium chloride

methyl 6-chloromethylpyridine-2-carboxylate

→

title compound

Yield 9.4%

Methyl 6-(5-methoxy-2-phenylindol-1-ylmethyl)pyridine-2-carboxylate

Yield 9.4%

Solvents

N,N-dimethylformamide

ethyl acetate

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   Temperaturecooling
3. 3
   workup.STIRRINGstirred for 30 minutes at room temperature
4. 4
   workup.STIRRINGby stirring at 80° C. for 18 hours
5. 5
   Otherto separate the organic layer
6. 6
   ExtractionThe aqueous layer was extracted twice with ethyl acetate
7. 7
   WashThe combined organic layer was washed with saturated brine
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    OtherThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Procedure

Under an argon atmosphere, to a solution of 5-methoxy-2-phenyl-1H-indole (582 mg) in N,N-dimethylformamide (13 mL) was added sodium hydride (dispersed in liquid paraffin, 55% or more, 171 mg) under ice-cooling. This mixture was stirred for 5 minutes under ice-cooling, and then stirred for 30 minutes at room temperature. Subsequently, methyl 6-chloromethylpyridine-2-carboxylate (483 mg) was added thereto, followed by stirring at 80° C. for 18 hours. The reaction mixture was poured into an ice-cooled saturated aqueous ammonium chloride solution, and then ethyl acetate was added to the mixture to separate the organic layer. The aqueous layer was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (91 mg). 1H-NMR (CDCl3) δ ppm: 3.87 (3H, s), 4.02 (3H, s), 5.58 (2H, s), 6.60-6.75 (2H, m), 6.81 (1H, dd, J=2.5, 8.8 Hz), 7.02 (1H, d, J=8.8 Hz), 7.15 (1H, d, J=2.5 Hz), 7.30-7.45 (5H, m), 7.60-7.70 (1H, m), 7.95-8.05 (1H, m).

Source