Ammonia → HCID 68865327, compound

Temperature

100 °C

Anhydrous ammonia gas was bubbled into a cold (0° C.) solution of (5S)-1-Ethyl-5-methylpiperazin-2-one hydrochloride (5.8 g, 32.3 mmol) in chloroform for 30 minutes. The resultant slurry was filtered and concentrated under vacuum. The residual oil was concentrated as a solution in toluene under vacuum, redissolved in toluene (120 mL) and treated with diethyl ethoxymethylenemalonate (7.0 g, 32.3 mmol) and heated in a sealed flask in an oil bath at 100° C. overnight. The resultant solution was concentrated under vacuum. The residual oil was concentrated as a solution in toluene under vacuum to provide the corresponding diethyl{[(2S)-4-ethyl-2-methyl-5-oxopiperazin-1-yl]methylene}malonate. Without further purification, to a solution of the malonate (10.5 g, 33.5 mmol) in anhydrous THF (330 mL) warmed with an external oil bath at 65° C. under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide (35.1 mL, 1 M, 35.1 mmol) was added. The solution was heated at the same temperature for one hour and concentrated under vacuum. The residue was partitioned between dichloromethane and hydrochloric acid (1M). The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether. The solid precipitated was filtered, washed with diethyl ether to provide the title compound as pale brown solid.

1. filtrationThe resultant slurry was filtered
2. concentrationconcentrated under vacuum
3. concentrationThe residual oil was concentrated as a solution in toluene under vacuum
4. dissolutionredissolved in toluene (120 mL)
5. concentrationThe resultant solution was concentrated under vacuum
6. concentrationThe residual oil was concentrated as a solution in toluene under vacuum

ORD record

ord-8776094dec6841dba19854b840aacf10

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538112B2