1H-Indole, 2,6-dimethyl- → 1,2-Dimethylindole

Participants

Reaction Steps

2,6-Dimethyl-1H-indole. A solution of 1.3M sec-butyl lithium/cyclohexane (81.0 ml, 0.105 mol) was added slowly to 11.05 g (0.05 mol) of N-tert-butoxycarbonyl-4-ethoxy-2-methylaniline in 150 ml of THF while keeping the temperature below −40° C. with a dry ice-ethanol bath. After 0.25 hours, 7.21 g (0.07 mol) of N-methoxy-N-methylacetamide in an equal volume of THF was added dropwise. The reaction mixture was stirred for 1 hour, the cooling bath removed and stirred an additional one hour. It was then poured into a mixture of 500 ml of ether and 500 ml of 1N HCl. The organic layer was separated, washed with water and dried over Na2SO4. After removing the solvent there remained 12.5 g of crude 1-(2-tert-butoxycarbonylamino-4-methylphenyl)-2-propanone. This material and 15 g of trifluoroacetic acid in 250 ml of CH2Cl2 was stirred at room temperature for 16 hours. The mixture was washed twice with water, a saturated Na2CO3 solution and dried over Na2SO4. After removing the solvent, the product was chromatographed on silica eluting with toluene to give 3.2 g (44% yield) of 2,6-(dimethyl-1H-indole melting at 74-76° C.

Provenance & Evidence