Ethyl chloroacetate → (R)-5-isopropylmorpholin-3-one

To an ice cold, stirred suspension of sodium hydride (60% in oil, 1.6 g, 40.0 mmol) in toluene (52 mL) was added dropwise a solution of (R)-2-amino-3-methylbutan-1-ol (1.8 g, 17.0 mmol) in toluene (38 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (8 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid ammonium chloride (2.1 g, 40.0 mmol) added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 95:5 dichloromethane/methanol) to give (R)-5-isopropylmorpholin-3-one (1.7 g, 68%) as a light yellow solid.

1. additionAfter the addition
2. temperatureat reflux for 20 h
3. temperaturecooled to room temperature
4. stirringThe mixture was stirred for 20 min
5. concentrationconcentrated under reduced pressure
6. customThe crude material was purified by column chromatography (silica gel, 95:5 dichloromethane/methanol)

ORD record

ord-1ac3f27640fa4feab989f0cad3520d8e

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863271B2