An improved synthesis of captopril.
An improved synthesis of captopril using methacrylic acid as the starting material is described. Treatment of methacrylic acid (I) with a hydrogen halide gave the 3-halogeno-2-methylpropanoic acids II and III, which were treated with thionyl chloride to yield the corresponding 3-halogeno-2-methylpropanoyl chlorides IV and V. Treatment of IV or V with L-proline yielded the N-(R,S-3-halogeno-2-methylpropanoyl)-L-prolines VI and VII, which were separated into optically pure R- and S-diastereoisomers using dicyclohexylamine. Treatment of halides of VI or VII with methanolic ammonium hydrosulfide gave captopril in 28% yield.
D002216:Captopril / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D008689:Methacrylates; D011392:Proline / Q000031:analogs & derivatives*
D008689:Methacrylates; C008384:methacrylic acid; D011392:Proline; D002216:Captopril