Hydrochloric Acid → 3-Methyl-2-oxoimidazolidine-4-carboxylic acid

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A solution of 5-methyl 1-(phenylmethyl)2-oxo-1,5-imidazolidinedicarboxylate (5 g, 18 mmol) (prepared as described in step (i) of Example 1, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) in dimethylformamide (27 ml) was added dropwise to a suspension of sodium hydride (60% in oil, 0.72 g, 18 mmol) in dimethylformamide (45 ml) at 0° C. under an argon atmosphere. The cooling bath was removed and the mixture stirred under argon for 1 hr then treated with methyl iodide (5.6 ml). The mixture was stirred at 22° C. for a further 18 hrs and then reduced in vacuo to give a residue which was partitioned between ethyl acetate (250 ml) and brine (75 ml). The organic layer was separated, using a hydrophobic frit, and then reduced in vacuo to give an orange oil. The oil was purified flash-silica gel column chromatography, eluting with 30% ethyl acetate in hexanes (3 column volumes) and then with a 30-70% gradient of ethyl acetate in hexanes (10 column volumes), to give 4-methyl 1-(phenylmethyl)3-methyl-2-oxo-1,4-imidazolidinedicarboxylate (3.65 g) as a colourless oil. (ii) 4-Methyl 1-(phenylmethyl)3-methyl-2-oxo-1,4-imidazolidinedicarboxylate (3.65 g, 12.5 mmol) was dissolved in methanol (300 ml) and hydrogenated in the presence of 10% palladium on carbon (0.5 g). The mixture was stirred for 18 hrs at 22° C., then filtered and reduced in vacuo to give methyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (1.90 g) as a white solid which was used in the next step without further purification. (iii) Methyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (0.150 g, 0.948 mmol) was dissolved in a 3:2 mixture of tetrahydrofuran and water respectively (2.5 ml) and cooled to 0° C. The mixture was then treated with lithium hydroxide (0.068 g, 2.84 mmol) and stirred with ice/water cooling for a further 5 hrs. The mixture was acidified to pH1 by addition of 2N hydrochloric acid (3 ml) and the resulting mixture was then reduced in vacuo to give 3-methyl-2-oxo-4-imidazolidinecarboxylic acid as a white solid (0.260 g) which was used without any further purification.

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