Continuous‐Flow Synthesis of (R)‐Tamsulosin Utilizing Sequential Heterogeneous Catalysis. Issue 13 (4th February 2022)

• Record Type: Journal Article
• Authors: Saito, Yuki; Nishizawa, Ken; Laroche, Benjamin; Ishitani, Haruro; Kobayashi, Shū
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 13(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-04
• Subjects: Continuous-Flow Synthesis -- Heterogeneous Catalysis -- Hydrogenation -- Multistep Flow Synthesis -- Reductive Amination; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202115643
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: We describe the continuous‐flow synthesis of ( R )‐tamsulosin, a blockbuster therapeutic drug employed for dysuria associated with urinary stones and benign prostatic hyperplasia, by utilizing sequential heterogeneous catalysis. Two heterogeneous catalysts have been developed for the synthesis, and the key step involves reductive amination of nitriles using dimethylpolysilane‐modified Pd on activated carbon/calcium phosphate. Overall, ( R )‐tamsulosin was obtained in 60 % yield and 64 % ee (99 % ee after recrystallization) in a flow stream through four catalytic transformations without the need for the isolation or purification of any intermediates or byproduct. Abstract : In a multistep continuous‐flow synthesis of (R)‐tamsulosin, three C−N bond formation/cleavage reactions with hydrogen gas over heterogeneous catalysts enabled the efficient construction of the key skeleton. Two different polysilane‐modified Pd catalysts were developed for these transformations, which were followed by a deprotection step under homogeneous catalysis to provide tamsulosin in 60 % overall yield in a flow stream.