sacubitril and carbene

A series of N-heterocyclic carbene (NHC)-palladium catalysts have been synthesized and applied to catalyze the Suzuki coupling reaction efficiently between aryl sulfonates and arylboronic acids with the potassium phosphate heptahydrate as a base. The desired yields are obtained even with less reactive aryl tosylates or aryl mesylates as substrates. This method was applied successfully to the synthesis of the (R)-2-(t-butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol which is the key intermediate of sacubitril, a component of the newly approved antihypertensive drug "Entresto."

Topics: Aminobutyrates; Antihypertensive Agents; Arylsulfonates; Biphenyl Compounds; Catalysis; Drug Combinations; Heterocyclic Compounds; Mesylates; Methane; Palladium; Phosphates; Potassium Compounds; Valsartan