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

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)

1. stirringstirring
2. waitwas carried out for 16 h at room temperature
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. washwashed with saturated sodium hydrogen carbonate solution (20 ml), saturated ammonium chloride solution (20 ml), water (20 ml) and saturated sodium chloride solution (20 ml)
5. dry with materialIt was then dried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customthe crude product was purified by column chromatography (silica gel, 2% methanol/dichloromethane)

ORD record

ord-ef6ee80b9a0a4297858f997e00a00d98

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680159B2