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

Autor: Sudhakaran S; Organometallic Synthesis and Catalysis Lab, Chemical Engineering Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Shinde PG; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Aratikatla EK; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Kaulage SH; Organometallic Synthesis and Catalysis Lab, Chemical Engineering Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Rana P; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Parit RS; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Kavale DS; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India., Senthilkumar B; Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India., Punji B; Organometallic Synthesis and Catalysis Lab, Chemical Engineering Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India.
Jazyk: angličtina
Zdroj: Chemistry, an Asian journal [Chem Asian J] 2022 Jan 03; Vol. 17 (1), pp. e202101208. Date of Electronic Publication: 2021 Dec 06.
DOI: 10.1002/asia.202101208
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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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