Trifluoroacetic acid methylene chloride → HCID 131728810, compound

Participants

Reaction Steps

To a stirred solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (1.0 g, 5 mmol) (prepared as described in step (iii) of Example 13) in N,N-dimethylformamide (20 ml) at 0° C. was added sodium hydride (60% dispersion in oil) (220 mg, 5.5 mmol). After 10 minutes a solution of 4-(2-chloroethyl)morpholine (898 mg, 6 mmol) in N,N-dimethylformamide (2 ml) and potassium iodide (166 mg, 1 mmol) was added and the mixture was heated at 70° C. for 2 hours. After cooling to room temperature water was added and the mixture was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organic extracts were separated, washed with water and brine, dried and evaporated. The residue was purified by silcia gel chromatography eluting with 5-10% 2M ammonia in methanol and dichloromethane to give 1,1-dimethylethyl-3-methyl-1-[2-(4-morpholinyl)ethyl]-2-oxo-4-imidazolidinecarboxylate (740 mg, 47%) as an oil. LC/MS [M+H]+=314. (ii) A solution of 1,1-dimethylethyl-3-methyl-1-[2-(4-morpholinyl)ethyl]-2-oxo-4-imidazolidinecarboxylate (740 mg, 2.361 mmol) in TFA/DCM (1:2, 6 ml) was stirred at room temperature for 5 hours. The solution was evaporated and the residue was co-evaporated with DCM and dried to give crude 3-methyl-1-[2-(4-morpholinyl)ethyl]-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜2.3 mmol) which was used in the next step. LC/MS [M+H]+=258.

Provenance & Evidence