Propanoic acid, 3-[[(4-chlorophenyl)methyl]amino]-3-oxo-, methyl ester synthesis

Yield:1466514-73-7 81.3%

Reaction Conditions:

with triethylamine in dichloromethane at -78; for 0.666667 h;

Steps:

1 Preparation of methyl 3-{[(4-chlorophenyl)methyl]amino}-3-oxopropanoate, (3a).

To a solution of 4-chlorobenzylamine (1a) (7.8 mL, 57.5 mmol) in DCM was added Et3N (24 mL, 172.6 mmol) and the mixture was cooled in a -78 °C bath. A solution of methyl 3- chloro-3-oxopropionate (2a) (7.0 mL, 57.5 mmol) in DCM (20 mL) was added via a dropping funnel over 10 min. The mixture was stirred at -78 °C for 30 min and then it was slowly warmed to room temperature. After overnight, the reaction was quenched with saturated NaHCO₃ solution. The layers were separated and the organic layer was washed with brine, dried over Na₂SO₄, filtered and concentrated under reduced pressure. The solid was suspended in ~10 mL EtOAc and further diluted with 200 mL hexanes. The resulting precipitate was filtered, washed with hexanes providing (3a) as a light yellow solid (11.3 g, 81.3% yield).

References:

WO2021/174355,2021,A1 Location in patent:Page/Page column 86-88