Réaction #2487470

Équation de réaction

methyl 6-chloromethylpyridine-2-carboxylate

ammonium chloride

2-(butan-2-yl)-6-chloro-5-methoxy-1H-indole

sodium hydride

→

title compound

Rendement 69.7%

Methyl 6-[2-(butan-2-yl)-6-chloro-5-methoxyindol-1-ylmethyl]pyridine-2-carboxylate

Rendement 69.7%

Solvants

water

N,N-dimethylformamide

Conditions de réaction

Traitement

1. 1
   Températurecooling
2. 2
   Températurecooling
3. 3
   workup.STIRRINGby stirring at 80° C. for 21 hours
4. 4
   Extractionfollowed by extraction with ethyl acetate
5. 5
   LavageThe organic layer was washed with water and saturated brine successively
6. 6
   Séchagedried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   AutreThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Mode opératoire

To a solution of 2-(butan-2-yl)-6-chloro-5-methoxy-1H-indole (289 mg) in N,N-dimethylformamide (6.1 mL) was added sodium hydride (dispersed in liquid paraffin, 55% or more, 73 mg) under ice-cooling. This mixture was stirred for 1 hour under ice-cooling. Subsequently, methyl 6-chloromethylpyridine-2-carboxylate (271 mg) was added thereto, followed by stirring at 80° C. for 21 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous ammonium chloride solution/water (2/1, 30 mL) was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, 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 (328 mg). 1H-NMR (CDCl3) δ ppm: 0.84 (3H, t, J=7.4 Hz), 1.23 (3H, d, J=6.9 Hz), 1.45-1.80 (2H, m), 2.60-2.75 (1H, m), 3.93 (3H, s), 4.06 (3H, s), 5.50 (2H, s), 6.31 (1H, s), 6.40-6.50 (1H, m), 7.12 (1H, s), 7.15 (1H, s), 7.64 (1H, t, J=7.9 Hz), 7.95-8.05 (1H, m).

Source