methyl 2-(2,5-dioxoimidazolidin-4-yl)acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2,5-dioxo-imidazolidin-4-yl)-acetic acid methyl ester (6.48 g, 37.6 mmol) in DMF (250 mL) is treated with 2-(bromomethyl)-napthalene (9.15 g, 41.4 mmol), MgSO4 (4.53 g, 37.6 mmol) and then K2CO3 (15.61 g, 0.113 mol) at 0° C. The resultant mixture is warmed to room temperature and stirred under N2 for 16 hours. The reaction mixture is filtered, and then aqueous 1N HCl (300 mL) is added to the filtrate. The filtrate is extracted with Et2O and the organic layer dried. The solvent is removed to give a crude oil which is purified by flash chromatography using 2:1 hexanes:acetone to afford 6.27 g of (1-naphthalen-2-ylmethyl-2,5-dioxo-imidazolidin-4-yl)-acetic acid methyl ester (53%). Rf=0.32 (1:1 hexanes:acetone). 1H NMR. at 0° C The reaction mixture is filtered aqueous 1N HCl (300 mL) is added to the filtrate The filtrate is extracted with Et2O the organic layer dried The solvent is removed to give a crude oil which is purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2,5-dioxo-imidazolidin-4-yl)-acetic acid, methyl ester (2.35 g, 13.7 mmol) in DMF (100 mL) is treated with p-methyl benzyl bromide (2.90 g, 15.7 mmol), MgSO4 (3.30 g, 27.4 mmol) and then K2CO3 (3.77 g, 27.3 mmol). The resultant mixture is stirred under N2 in an ice bath for 30 minutes and then warmed to room temperature for 16 h. The reaction mixture is then filtered, and then aqueous 1N HCl (150 mL) is added to the filtrate. The filtrate is extracted with EtOAc and the organic layer dried. The solvent is removed to give 4.11 g crude product which is purified by flash chromatography using 100% CH2Cl2 then 97.5:2.5 CH2Cl2:MeOH to give 3.67 g (97%) [1-(4-methyl-benzyl)-2,5-dioxo-imidazolidin-4-yl]-acetic acid methyl ester. 1H NMR. MS (ES+) Calc'd for C14H17N2O4 (M+1) 277. Found m/z 277 (100%). The reaction mixture is then filtered aqueous 1N HCl (150 mL) is added to the filtrate The filtrate is extracted with EtOAc the organic layer dried The solvent is removed to give 4.11 g crude product which is purified by flash chromatography

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2,5-dioxo-imidazolidin-4-yl)-acetic acid methyl ester (26.6 g, 0.155 mol) in DMF (500 mL) was treated with 4-methoxybenzyl chloride (26.6 g, 0.170 mol), MgSO4 (18.6 g, 0.154 mol) and then 325 mesh K2CO3 (42.71 g, 0.309 mol) at 0° C. The resultant mixture was warmed to room temperature under N2 and then heated at 45° C. for 4 h. The reaction mixture was filtered, and then aqueous 1N HCl (200 mL) was added to the filtrate. The filtrate was extracted with EtOAc and the organic layer dried (MgSO4). The solvent was removed in vacuo to give 11.43 g crude product which was purified by flash chromatography using a gradient of 3:1 to 1:1 hexanes:acetone to give 9.81 g (22%) [1-(4-methoxy-benzyl)-2,5-dioxo-imidazolidin-4-yl]-acetic acid methyl ester. MS (ES+) Calc'd for C14H17N2O5 (M+1) 293. Found m/z 293 (100%). 1H NMR. at 0° C The reaction mixture was filtered aqueous 1N HCl (200 mL) was added to the filtrate The filtrate was extracted with EtOAc the organic layer dried (MgSO4) The solvent was removed in vacuo to give 11.43 g crude product which was purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Hydantoin acetic acid (20.57 g, 0.130 mol) in MeOH (210 mL) was treated with conc. H2SO4 (7 mL) and heated to reflux under N2 for 2.5 h. The resultant clear solution was cooled and the solvent removed in vacuo to give an oil which was diluted with water (65 mL) and extracted 4 times with EtOAc. The organic layer was dried (MgSO4) and the solvent removed in vacuo to afford 19.81 g (88%) of (2,5-dioxo-imidazolidin-4-yl)-acetic acid methyl ester. MS (ES+) Calc'd for C6H9N2O4 (M+1) 173. Found m/z 173 (100%). 1H NMR. heated to reflux under N2 for 2.5 h The resultant clear solution was cooled the solvent removed in vacuo to give an oil which extracted 4 times with EtOAc The organic layer was dried (MgSO4) the solvent removed in vacuo