反应详情

1-Methyl-2-piperidinemethanol (0.459 g, 3.580 mmol, 1 eq) was suspended in dry CH2Cl2 (5 mL). p-Toluenesulfonyl chloride (0.684 g, 3.580 mmol, 1 eq) and triethyl amine (1.00 mL, 7.160 mmol, 2 eq) were added. The reaction mixture was stirred at room temperature for 8 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was dissolved in dry acetonitrile (20 mL). 2-Methyl-3-benzyloxycarbonyl-5-hydroxyindole (1.005 g, 3.580 mmol, 1 eq) and Cs2CO3 (1.159 g, 3.580 mmol, 1 eq) were added. The reaction mixture was stirred and heated to reflux for 16 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.200 g (15%) of the indole-piperidine ether was obtained as a brown solid. This was converted to the .HCl salt. LC/MS (ESI+) 393 (M+1); Anal. Calcd for C24H28N2O3.HCl.0.8H2O: C, 65.02; H, 6.96; N, 6.32; Found: C, 65.36; H, 7.02; N, 5.96.

1. customThen the reaction was quenched with saturated sodium bicarbonate
2. extractionextracted with ethyl acetate (3×)
3. washThe combined organic phases were washed with brine
4. dry with materialdried over Na2SO4
5. customAfter removing the solvent
6. dissolutionthe residue was dissolved in dry acetonitrile (20 mL)
7. stirringThe reaction mixture was stirred
8. temperatureheated
9. temperatureto reflux for 16 hours
10. customThen the reaction was quenched with saturated sodium bicarbonate
11. extractionextracted with ethyl acetate (3×)
12. washThe combined organic phases were washed with brine
13. dry with materialdried over Na2SO4
14. customAfter removing the solvent
15. customchromatographed
16. washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)