Methyl malonyl chloride → Methyl 3-((2-fluorophenyl)(methyl)amino)-3-oxopropanoate

Temperatur

0 °C

To a solution of methyl 3-chloro-3-oxopropanoate (1.75 mL, 15.99 mmol) in dry DCM (32 ml) was added 2-fluoro-N-methylaniline (2 g, 15.99 mmol) and the reaction mixture was stirred at 0° C. for 1 h, evaporated then redissolved in EtOAc, washed with dilute NaHCO3, and brine. The organic phase was dried over sodium sulfate, and concentrated under reduced pressure to afford methyl 3((2-fluorophenyl)(methyl)amino)-3-oxopropanoate as yellow oil which was used without further purification (3.3 g, 16 mmol, 97%, crude). To a solution of this material (3.3 g, 16 mmol) in THF (16 ml) and water (16 ml) was added LiOH H2O (1.35 g, 31.5 mmol) and the reaction mixture was stirred overnight, evaporated (to remove the THF) and then extracted with EtOAc. The aqueous phase was acidified to pH˜1 by addition of 1N HCl and extracted with EtOAc. The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title compound 245 as a brown solid, which was used without further purification (2.75 g, 13.03 mmol, 81% yield). MS (m/z): (M+1) 218.0 (88%), (2M+Li) 429.0 (100%).

1. customevaporated
2. dissolutionthen redissolved in EtOAc
3. washwashed with dilute NaHCO3, and brine
4. dry with materialThe organic phase was dried over sodium sulfate
5. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-f57b3df62f9a46a3acfe93c945b9a133

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08329726B2