3-chloro-N'-hydroxy-4-propan-2-yloxybenzenecarboximidamide → 3-(3-Chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole

Participants

Reaction Conditions

Reaction Steps

In a 25 mL microwave tube 4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoyl chloride (0.483 g, 1.784 mmol) and (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.272 g, 1.189 mmol) in pyridine (15 mL) were combined to give an orange solution. The vessel was capped and the reaction heated at 200° C. for 20 min under microwave irradiation (Biotage Optimizer, 300 W). The mixture was cooled, the solvent was removed to afford a yellow solid, which was partitioned between water (100 mL) and EtOAc (50 mL), extracted by EtOAc (2×30 mL), the combined EtOAC layer was washed by water (2×30 mL), and concentrated to afford a yellow solid, which was purified via silica gel chromatography (40 g, 30% EtOAc:Heptane) to afford 3-(3-chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole (0.3 g, 0.674 mmol, 56.7% yield) as white solid. LC/MS (30—95 NH4OAc 4m GC8.olp) Rt=3.22 min.; MS m/z: 445.31 (M+H)+. 1H NMR (400 MHz, Solvent d-DMSOδ ppm 8.17-8.09 (m, 2H), 8.05 (d, J=2.13 Hz, 1H), 7.99 (dd, J=8.64, 2.15 Hz, 1H), 7.38 (d, J=9.01 Hz, 1H), 7.26-7.19 (m, 2H), 4.88-4.77 (m, 1H), 4.45 (s, 1H), 4.23-4.07 (m, 3H), 3.79 (dd, J=8.42, 6.29 Hz, 1H), 1.35 (m, 12H).

Provenance & Evidence