2-(4-Fluorophenyl)acetic acid → 2-(4-Fluorophenyl)-N-methoxy-N-methylacetamide

To a stirred solution of 2-(4-fluorophenyl)acetic acid (15 g, 97.32 mmol, 1.00 equiv) in CH2Cl2 (300 mL) was added methoxy(methyl)amine hydrochloride (11.1 g, 113.79 mmol, 1.20 equiv), 4-dimethylaminopyridine (12 g, 98.22 mmol, 1.00 equiv), 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (28.2 g, 147.10 mmol, 1.50 equiv), and DIEA (37.5 g, 290.14 mmol, 3.00 equiv). The resulting solution was stirred at room temperature for 16 h and then diluted with EtOAc (150 mL). The organics were washed with aqueous 1N HCl (2×150 mL) and brine (2×150 mL). It was then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography (silica gel, eluting with EtOAc/petroleum ether (1:3)). This resulted in 18 g (88%) of the title compound as yellow oil. 1H-NMR (400 MHz, CDCl3): δ ppm 7.29-7.25 (m, 211), 7.03-6.99 (m, 2H), 3.75 (s, 2H), 3.65 (s, 3H), 3.21 (s, 3H).

1. washThe organics were washed with aqueous 1N HCl (2×150 mL) and brine (2×150 mL)
2. dry with materialIt was then dried over anhydrous Na2SO4
3. concentrationconcentrated under reduced pressure
4. customThe crude residue was purified by flash chromatography (silica gel, eluting with EtOAc/petroleum ether (1:3))

ORD record

ord-949b4a44b88c479688aef312e23a14c5

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181200B2