Tetrahydrofuran → HCID 18359216, compound

Participants

Reaction Conditions

Reaction Steps

2-(2-Bromoethyl)-1,3-dioxolane (2.9 mL, 25 mmol) was added to Mg (0.7 g, 29 mmol) and THF (50 mL) and heated to 30° C. for 1.5 h under nitrogen atmosphere. A solution of thiophen-3-yl-(1-tritylimidazol-4-yl)methanone (4.69 g, 11.2 mmol) in THF (15 mL) was added slowly and the reaction was heated for 18 h at 30° C. The reaction was diluted with EtOAc, washed with NH4Cl (sat'd), water, and brine. The organic layer was dried with MgSO4, filtered and the solvent was evaporated in vacuo to yield 3-(1,3-dioxan-2-yl)-1-(1-tritylimidazol-4-yl)-1-(thiophen-3-yl)-propan-1-ol as ton crystals (6.01 g, 90%). mp 120-123° C. A solution of this material (1 g, 1.86 mmol) in dichloroethane (10 mL) was added to trimethylsilyl trifluoromethanesulfonate (0.36 mL, 18.6 mmol) and dichloroethane (50 mL) at 0° C. After stirring for 3 h at 25° C. the reaction mixture was cooled to 0° C. and treated with Na2CO3 (sat'd). The organic layer was dried with MgSO4, filtered and solvent was evaporated in vacuo. Purification by chromatography using EtOAc/MeOH/NH4OH, 98:1.9:0.1 as eluant afforded 4-(thionaphth-4-yl)imidazole (0.146 g, 40%). 1H NMR (CD3OD) δ7.31 (t, 1H), 7.40 (s, 1H), 7.60 (d, 1H), 7.61 (d, 1H), 7.77 (d, 1H), 7.80 (s, 1H), 7.83 (d, 1H). This material (0.146 g, 0.73 mmol) was dissolved in hot isopropyl alcohol (4 mL) and treated with maleic acid (0.847 g, 0.73 mmol) to yield Cp-1 (0.23 g, 100%) mp 173-174° C. 1H NMR (DMSO) δ6.12 (s, 2H), 7.45 (t, 1H), 7.68 (d, 1H), 7.88 (d, 1H), 7.90 (d, 1H), 7.92 (s, 1H), 8.05 (d, 1H), 8.62 (s, 1H). MS m/e 201 (M+H), 100.

Provenance & Evidence