Acetamidomalonic acid diethyl ester → HCID 10501146, compound

A mixture of diethyl acetamidomalonate (1.6 g, 7.4 mmol) and potassium tert-butoxide (0.9 g, 8.0 mmol) in N-methylpyrrolidone (30 mL) was stirred at room temperature for 30 min. Ethyl 4-(bromomethyl)-3-methoxyisoxazole-5-carboxylate (1.8 g, 6.8 mmol) in N-methylpyrrolidone (10 mL) was added (temp 22-28° C.) and the resulting mixture was stirred at room temperature for 1.5 h. The reaction mixture was poured onto an ice/water mixture (100 mL) and the aqueous phase was extracted with EtOAc (3×150 mL). The organic extracts were washed with an aqueous solution of potassium tert-butoxide, water (100 mL) and brine (100 mL), dried (MgSO4) and concentrated in vacuo. Flash chromatography (silica gel, eluent: EtOAc/heptane=1:1) afforded crude title compound (1.8 g, 66%). A small sample was recrystallized (EtOAc/heptane) to give colourless crystals: mp 78-80° C. The crude product was used in the next step without further purification.

1. stirringthe resulting mixture was stirred at room temperature for 1.5 h
2. extractionthe aqueous phase was extracted with EtOAc (3×150 mL)
3. washThe organic extracts were washed with an aqueous solution of potassium tert-butoxide, water (100 mL) and brine (100 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo

ORD record

ord-5b0e4d0de62b40f3884f286a300d088f

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06200999B1