Nickel‐Catalyzed Asymmetric Hydrogenation for the Synthesis of a Key Intermediate of Sitagliptin.

Autor:	Sudhakaran, Shana, Shinde, Prasad G., Aratikatla, Eswar K., Kaulage, Sandeep H., Rana, Priksha, Parit, Ratan S., Kavale, Dattatry S., Senthilkumar, Beeran, Punji, Benudhar
Předmět:	ASYMMETRIC synthesis ENAMINES SITAGLIPTIN RESOLUTION (Chemistry) HYDROGENATION NICKEL catalysts HYPOGLYCEMIC agents
Zdroj:	Chemistry - An Asian Journal; 1/3/2022, Vol. 17 Issue 1, p1-6, 6p
Abstrakt:	Nickel‐catalyzed enantioselective hydrogenation of enamines leading to the efficient synthesis of 3‐R‐Boc‐amino‐4‐(2,4,5‐trifluorophenyl)butyric esters, the key intermediate of the blockbuster antidiabetic drug (R)‐SITAGLIPTIN, is described. The sitagliptin motifs were isolated in more than 99% yield and with 75–92% ee using the earth‐abundant nickel catalyst. Upon chiral resolution with (R)‐ and (S)‐1‐phenylethylamines, the partially enantioenriched (R)‐ and (S)‐Boc‐3‐amino‐4‐(2,4,5‐trifluorophenyl)butanoic acids provided >99.5% ee of the crucial sitagliptin intermediate. The asymmetric hydrogenation protocol was scaled up to 10 g with consistency in yield and ee, and has been reproduced in multiple batches. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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