Diisopropylethylamine → 2-(2-Cyclobutoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

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Reaction Steps

A 25 mL vial containing a stirring bar is charged with 2-cyclobutoxy-3-methyl-benzoic acid (1.01 g, 4.87 mmol) and dry DCM (14 mL). Stirring is initiated. HBTU (1.84 g, 4.86 mmol) is added. After 5 min, the 2-aminoindane-2-carboxylic acid ethyl ester (1 g, 4.87 mmol) is added followed by the DIPEA (1.9 mL, 10.92 mmol). The reaction is allowed to stir for 12 days. Analysis by tlc of the reaction mixture (silica, 10% MeOH/DCM) indicates complete consumption of the starting amine. The contents of the reaction flask are diluted with EtOAc (70 mL) and transferred to a separatory funnel. This is washed consecutively with dilute aqueous HCl (3%, 35 mL), saturated aqueous NaHCO3 (35 mL) and brine (35 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 2.56 g of an off-white solid. This material is dissolved in 15 mL of DCM. This is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 10% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 50% over 10 column volumes and then 100% EtOAc for 2 column volumes with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 7 through 22 are combined and evaporated in vacuo. Pumping to a constant weight gives amorphous white solid 1.73 g.

Provenance & Evidence