Potassium Phosphate, Tribasic → HCID 118062400, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (R)-1-phenylethyl 4-(4-bromophenyl)-1-methyl-1H-1,2,3-triazol-5-ylcarbamate (120 mg, 0.3 mmol), ethyl 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylic acid ethyl ester (142 mg, 0.449 mmol), palladium(II) acetate (10.1 mg, 0.05 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (36.8 mg, 0.1 mmol), and potassium phosphate tribasic (190 mg, 0.9 mmol) in a vial were added toluene (2.25 mL) and water (0.5 mL) at room temperature under nitrogen atmosphere. The resulting light brown suspension was disconnected from the nitrogen line and the reaction mixture was heated to 105° C. and the progress of the reaction was followed by TLC analysis and it was completed after 1 h at this temperature. Then, it was cooled to room temperature and diluted with water and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude compound which was purified using an ISCO (40 g) column chromatography eluting with 0-70% ethyl acetate in hexanes. The desired fractions were combined and the solvent was removed under vacuum to obtain (R)-1-(4′-(1-methyl-5-((1-phenylethoxy)-carbonylamino)-1H-1,2,3-triazol-4-yl)biphenyl-3-yl)cyclopropanecarboxylic acid ethyl ester as a white solid (94 mg, 61% yield). LC/MS calcd. for C30H30N4O4 (m/e) 510.0, obsd. 511.1 (M+H, ES+).

Provenance & Evidence