Toluene → 2-(3-Methyl-2-prop-2-ynyloxy-benzoylamino)-indan-2-carboxylic acid ethyl ester

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Reaction Steps

A 100 mL round bottom flask containing the 2-(hydroxy-3-methyl-benzoyl)-indan-2-carboxylic acid ethyl ester (3) (0.29 g 0.855 mmol) is charged with DMF (4 mL) and a stirring bar is added. After dissolution of the starting material, K2SO4 (0.3 g, 2.17 mmol) is added followed by a solution of propargyl bromide in toluene (11.59 M, 240 μL, 2.78 mmol). After stirring for 62 h tlc analysis (silica, 1:1 EtOAc/heptanes) indicates that the starting material had been consumed. The material is cleanly converted to a UV positive spot with a slightly lower Rf. The reaction is diluted with EtOAc (80 mL) and filtered through a pad of Celite. The filtrate is transferred to a reparatory funnel. This is washed repeatedly with a saturated aqueous solution of NaHCO3 (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and evaporated in vacuo to yield 2.09 g of a light brown oil. This is purified (silica, 40 g ISCO column 10% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 50% EtOAc in heptanes for 10 column volumes). 17 mL fractions of UV positive eluent are collected. Fractions 4 through 10 are combined, evaporated in vacuo and pumped to constant weight to give 0.21 g of white solid.

Provenance & Evidence