4-Toluenesulfonyl chloride → Indole piperidine ether

Participants

Reaction Steps

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.

Provenance & Evidence