Urea → (7R,7aS)-4-(7-Hydroxy-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a suspension of compound 1E (0.145 g, 0.56 mmol) in CH2Cl2 (2 mL) cooled at 0° C. was added i-Pr2NEt (0.12 mL, 0.69 mmol). After stirring at 0° C. for 20 min, compound 2E (95 mg, 0.48 mmol) in CH2Cl2 (1 mL) solution was added, along with 4 Å molecular sieves (0.5 g) and the resulting mixture stirred at rt until urea formation was complete (˜2 h). To the mixture was then added DBU (0.15 mL, 1.0 mmol), the resulting brown colored suspension was stirred vigorously at rt until hydantoin formation was complete (˜15 h). The reaction mixture was loaded on a silica gel column, eluted with 40% EtOAc/hexane, and 5% MeOH in EtOAc/hexane (1:1) to afford 128 mg of the title compound as a white solid. HPLC: 99% at 2.42 min (retention time) (Conditions: Phenom. Luna C18 (4.6×50 mm); Eluted with 0% to 100% B; 4 min gradient (A=90% H2O—10% MeOH—0.1% H3PO4 and B=10% H2O—90% MeOH—0.1% H3PO4 ), Flow rate at 4 mL/min., UV detection at 220 nm). Chiral HPLC: retention time=9.01 min (99%); Conditions: (CHIRALPAK® OD column 4.6×250 mm; 25% isopropanol in hexane over 30 min at flow rate 1.0 mL/min, UV detection at 220 nm); MS (ES) m/z 312 [M+1]+

Provenance & Evidence