Epichlorohydrin → HCID 58044386, compound

Participants

Reaction Conditions

Reaction Steps

4,5-dichloro-2-methoxyphenol (200.0 mg, 1.036 mmol), epichlorohydrin (958.6 mg, 10.36 mmol, 10 equiv.) and K2CO3 (1.43 g, 10.36 mmol, 10 equiv.) were placed in a 50 mL round bottomed flask under a nitrogen atmosphere. To the flask were added DMF (3 mL) at ambient temperature. The mixture was heated at 70° C. for 16 hour. To the mixture was added water (30 mL). And then the whole was extracted with EtOAc (30 mL×3). Combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure. Crude product (2-((4,5-dichloro-2-methoxyphenoxy)methyl)oxirane, 248.7 mg, 0.998 mmol, 96.4%) was used for the subsequent step without further purification. 6-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (47.2 mg, 0.169 mmol), 2-((4,5-dichloro-2-methoxyphenoxy)methyl)oxirane (50.5 mg, 0.2028 mmol, 1.2 equiv.) and K2CO3 (46.8 mg, 0.339 mmol, 2.0 equiv.) were placed in a 50 mL round bottomed flask under a nitrogen atmosphere. To the flask were added DMF (3 mL) at ambient temperature. The mixture was heated at 80° C. for 1 hour. The mixture was filtered through Celite and the filtrate was injected to preparative HPLC to give compound 198 as a colorless oil (24.3 mg, 0.0460 mmol, 27.2%). LCMS (EI: 70 eV) 552 (M++2+Na), 551 (M++1+Na), 550 (M++Na), 530 (M++2), 529 (M++1), 528 (M+).

Provenance & Evidence