Nitro and related compounds

Adams, Joseph P.; Box, David S.

doi:10.1039/co9970400415

Cited by 10 publications

(1 citation statement)

References 125 publications

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“…However, an asymmetric synthesis analogous to Scheme was still lengthy, and the epoxide opening provided an isolation challenge (mandelic acid was used to aid the isolation). Based on the literature precedent for selective meta-nitration of 1-aminoindan an initial attempt to nitrate commercially available (1 R ,2 R )-1-amino-2-indanol ( 26 ) using standard nitration conditions afforded the nitrate ester 27 , isolated as the nitrate salt (Scheme ). This result was satisfying given the regiocontrol observed, but isolation of an intermediate with three nitro groups represented an unacceptable scale-up hazard .…”

Section: Resultsmentioning

confidence: 99%

Development of a Practical Synthesis of an Aminoindanol-Derived M1 Agonist

Hansen

Borders

Clayton

et al. 2009

Org. Process Res. Dev.

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An efficient and scalable synthesis of the clinical candidate 1 is described. The first-generation synthesis built the enantioenriched nitro-aminoindanol core from 6-nitroindanone using a five-step literature route. The second-generation route used a safe aromatic nitration protocol in the presence of the unprotected alcohol to afford the requisite nitro-aminoindanol in one step. Challenges addressed in the remainder of the synthesis include a nitro group reduction to afford ppm levels of unreacted Ar-NO 2 (a mutagen) and a novel amidine formation under mild conditions via DMAP/ K 2 CO 3 -promoted reaction with a thioimidate-activated amide. A convenient protocol for freebasing the API was provided by stirring with solid K 2 CO 3 and monitoring disappearance of HI by reverse-phase HPLC.

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Section: Resultsmentioning

confidence: 99%

Development of a Practical Synthesis of an Aminoindanol-Derived M1 Agonist

Hansen

Borders

Clayton

et al. 2009

Org. Process Res. Dev.

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Formation of Amines from Nitro Compounds

Larock

Pletnev

2018

Comprehensive Organic Transformations

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Michael Addition Initiated Carbocyclization Sequences with Nitroolefins for the Stereoselective Synthesis of Functionalized Heterocyclic and Carbocyclic Systems

Dumez

Durand

Guillaume

et al. 2009

Chemistry A European J

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The synthesis of various heterocycles and carbocycles (tetrahydrofurans, pyrrolidines, cyclopentanes) has been achieved by using new and efficient ionic addition/cyclization sequences. Nitroolefins play an important role in the Michael addition induced ring-closing reactions (MIRC) reported in the present article, with various substituted alcohols, amines, Grignard reactants, or malonate derivatives acting as the nucleophile partner. The optimized cascade reactions were high yielding in most cases and highly stereoselective, creating up to three stereogenic centers starting from achiral substrates.

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Nitro and related compounds

Cited by 10 publications

References 125 publications

Development of a Practical Synthesis of an Aminoindanol-Derived M1 Agonist

Development of a Practical Synthesis of an Aminoindanol-Derived M1 Agonist

Formation of Amines from Nitro Compounds

Michael Addition Initiated Carbocyclization Sequences with Nitroolefins for the Stereoselective Synthesis of Functionalized Heterocyclic and Carbocyclic Systems

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