Investigations into the Suzuki–Miyaura coupling aiming at multikilogram synthesis of E2040 using (o-cyanophenyl)boronic esters
| Autor: | Hiroyuki Naka, Katsuyuki Ogura, Mamoru Miyazawa, Yoshio Urawa, Shigeru Souda |
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| Rok vydání: | 2002 |
| Předmět: |
Steric effects
Aryl Organic Chemistry chemistry.chemical_element Phenylpiperazine Biochemistry Medicinal chemistry Toluene Inorganic Chemistry chemistry.chemical_compound chemistry Potassium phosphate Materials Chemistry Organic chemistry Physical and Theoretical Chemistry Triphenylphosphine Hydrate Palladium |
| Zdroj: | Journal of Organometallic Chemistry. 653:269-278 |
| ISSN: | 0022-328X |
| DOI: | 10.1016/s0022-328x(02)01175-0 |
| Popis: | The Suzuki–Miyaura cross-coupling reaction between 1-{3-bromo-4-chloro-5-[1-( R )-fluoropropyl]}phenylpiperazine (( R )- 1b ) and thermally unstable ( o -cyanophenyl)boronic ester 6b in the presence of dichlorobis(triphenylphosphine)palladium and potassium phosphate hydrate in boiling toluene was found to afford 1-{3-(2-cyanophenyl)-4-chloro-5-[1-( R )-fluoropropyl]}phenylpiperazine (( R )- 5 ), an intermediate for the synthesis of E2040, in excellent yields. The reaction conditions for the cross-coupling were optimized by the design of experiments (DOE) approach and found to be applicable to electron-rich and/or sterically hindered aryl bromides. Safety evaluation for the production of ( R )- 5 is also described. |
| Databáze: | OpenAIRE |
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