Large-Scale Synthesis of Enantio- and Diastereomerically Pure (<i>R</i>,<i>R</i>)-Formoterol

Hett, Robert; Fang, Q. Kevin; Gao, Yun; Wald, Stephen A.; Senanayake, Chris H.

doi:10.1021/op970116o

Cited by 79 publications

(52 citation statements)

References 12 publications

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“…The yield increased to 37% with 62% ee at a lower HCOOH/ NEt 3 ratio (1:1). 12 On the other hand, when sodium formate in water was selected as the hydrogen donor, Ru-and Rh-catalysts gave 86% ee and 92% ee, respectively, with good yield (entry 4,5). Under the same condition, the yield and enantioselectivity were slightly improved using Ru-and Rh-(S,S)-PEGBsDPEN as catalysts (entry 6, 7).…”

Section: Resultsmentioning

confidence: 99%

The asymmetric synthesis of (R,R)‐formoterol via transfer hydrogenation with polyethylene glycol bound Rh catalyst in PEG2000 and water

et al. 2009

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(R,R)-formoterol was synthesized in seven steps with 4-hydroxyl-3-nitro-acetophenone as the starting material. The key intermediate, the chiral secondary alcohol 4, was prepared via Rh-catalyzed asymmetric transfer hydrogenation with (S,S)-PEGBsDPEN as the ligand and sodium formate as the hydrogen donor under mild conditions. With a mixture of PEG 2000 and water as the reaction media, the catalyst system could be recycled four times.

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Section: Resultsmentioning

confidence: 99%

The asymmetric synthesis of (R,R)‐formoterol via transfer hydrogenation with polyethylene glycol bound Rh catalyst in PEG2000 and water

et al. 2009

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“…The b 2 headgroup 37 was prepared by an eight-step sequence, as shown in FiguRe 16. While this is a long linear sequence, the first six steps to the TBS-protected bromohydrin (35) are reasonably well precedented [30,33] and should be amenable to scale-up. The remaining two steps are similar to those used in the synthesis of the LABAs discussed earlier, and good yields were obtained for both steps.…”

Section: Future Science Groupmentioning

confidence: 99%

A Perspective on Synthetic and Solid-Form Enablement of Inhalation Candidates

Selby¹,

Koning

Roberts

2011

Future Med. Chem.

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The administration of compounds by a dry-powder inhaler presents significant challenges to the development and discovery chemist, owing to the stringent requirements placed upon the physical characteristics of the active pharmaceutical ingredient and the high complexity of the molecules concerned. The current state of synthetic chemistry technology is such that commercial syntheses of these compounds are demanding but achievable. While synthetic chemistry will remain a major component of the development of inhaled therapies, the main challenge facing practitioners in this area is the early identification of a suitable solid form. Further advances in the prediction of solid-form properties would significantly enable this field and may allow triage of molecules to be carried out at the design stage of projects.

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“…15. Reduction of aryl ketones: catalyst performance, development stage and company [44][45][46]. could be problematic (borate or silane hydrolysis products).…”

Section: Reduction Of Ketonesmentioning

confidence: 99%