An improved lanthanum catalyst system for asymmetric amination: toward a practical asymmetric synthesis of AS-3201 (Ranirestat).
A catalytic asymmetric amination with a lanthanum/amide complex was significantly improved. The use of lanthanum nitrate hydrate in place of lanthanum triisopropoxide made the process reproducible, scalable, and cost-effective. The development of a ternary catalytic system of La/ligand/amine was a key to high ee and catalytic turnover. A 100 g scale reaction was performed to showcase a practical synthesis of a key intermediate for AS-3201, a highly potent aldose reductase inhibitor.
Mashiko
Tomoyuki
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kumagai
Naoya
N
Shibasaki
Masakatsu
M
D000586:Amination; D002384:Catalysis; D007811:Lanthanum / Q000737:chemistry*; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism
D011719:Pyrazines; D013141:Spiro Compounds; D007811:Lanthanum; C115070:ranirestat