Hexane → 1-(1-Methyl-2-piperidyl)ethyl 1-methylindazole-3-carboxylate

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Reaction Steps

(1-Methyl-2-piperidyl)-1-ethanol (4.5 g, 31 mmol) was dissolved in dry THF (70 ml) and 1,3-dimethyl-2-imidazolidinone (20 ml) was added. The solution was ice-cooled and a hexane solution of n-BuLi (1.6M, 20 ml) was added dropwise. The reaction solution was stirred at room temperature for 20 minutes, to which was added dropwise a solution of 1 methylindazole-3-carboxylic acid chloride (5.4 g, 28 mmol) dissolved in a mixed solution of dry THF (70 ml) and 1,3-dimethyl-2-imidazolidinone (20 ml). The mixture was stirred overnight at room temperature, the reaction solution was concentrated under reduced pressure and a 5% sodium bicarbonate solution was added. It was extracted with chloroform. The organic layer was washed with a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a residue. Separation and purification of the residue by silica gel column chromatography (110 g SiO2, chloroform:methanol=100:1) and further silica gel column chromatography with a different solvent (100 g SiO2, hexane:ethyl acetate=1:1) gave the title compound, 0.52 g of a high polar isomer and 0.64 g of a low polar isomer, respectively.

Provenance & Evidence