Diisopropylethylamine → (R)-Methyl 3-(2-fluoro-2-methylpropanamido)-2,3-dihydro-1H-indene-5-carboxylate

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Reaction Steps

DIPEA (1.68 ml, 10.2 mmol, 3 eq) and HATU (1.29 g, 3.4 mmol, 1 eq) were added to a solution, cooled to 0° C., of 2-fluoro-2-methylpropanoic acid (360 mg, 3.4 mmol, 1 eq) in THF (15 ml). The reaction mixture was stirred for 15 min, then a solution of (R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (650 mg, 3.4 mmol, 1 eq) in THF (5 ml) was added and stirring was carried out for 16 h at room temperature. The reaction mixture was concentrated under reduced pressure, taken up in dichloromethane (50 ml) and washed with saturated sodium hydrogen carbonate solution (20 ml), saturated ammonium chloride solution (20 ml), water (20 ml) and saturated sodium chloride solution (20 ml). It was then dried over sodium sulfate and concentrated under reduced pressure, and the crude product was purified by column chromatography (silica gel, 2% methanol/dichloromethane). Yield: 52% (500 mg, 1.79 mmol)

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