Application of the asymmetric hydrogenation of enamines to the preparation of a beta-amino acid pharmacophore |
| |
| Institution: | 1. Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China;2. Key Laboratory of Preclinical Study for New Drugs of Gansu Province and Operative Surgery Institute, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China;1. College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao, 266042, China;2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing, 100050, China;1. Department of Chemical Engineering and Applied Chemistry, Chungnam National University, 99 Daehak-ro, Yuseong-Gu, Daejeon, 34134, Republic of Korea;2. Theoretical Physics Research Group, Ton Duc Thang University, Ho Chi Minh City, Viet Nam;3. Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam;4. Institute of Research and Development, Duy Tan University, Da Nang, Viet Nam |
| |
| Abstract: | (3R)-3-N-(tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 7a has been synthesized by an asymmetric hydrogenation of enamine ester 3 using chiral ferrocenyl ligands I and II in conjunction with Rh(COD)Cl]2. The direct reduction of 3 provides amino ester 1b in 93% ee, which was isolated as an (S)-camphorsulfonic acid salt to upgrade the enantiomeric excess to >99%. A more concise approach was developed involving the in situ protection of 1b using di-tert-butyldicarbonate. This approach provided the desired N-Boc amino ester 7b directly from the hydrogenation with 97% ee, which was upgraded to >99% ee upon crystallization. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
