Process Optimization for the Large-Scale Preparation of (2S,3aR,7aS)-tert-Butyl Hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists

doi:10.1021/ACS.OPRD.8B00208

Paper

Process Optimization for the Large-Scale Preparation of (2S,3aR,7aS)-tert-Butyl Hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists

Published Aug 28, 2018 · Lokesh Babu Jarugu, China Anki Reddy, Nanjundaswamy Kanikahalli Chikkananjunda

Organic Process Research & Development

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Abstract

An optimized large-scale synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate (1A), an important intermediate for nicotinic acetylcholine receptor agonists, is described. The key feature of the synthesis involves three transformations in a one-pot process, including debenzylation and ring hydrogenation of two fused bicyclic rings. Multihundred gram quantities of 1A were prepared.

Study Snapshot

The optimized large-scale synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate (1A) involves three transformations in a one

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Process Optimization for the Large-Scale Preparation of (2S,3aR,7aS)-tert-Butyl Hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists

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References

Novel tricyclic diamines 2. Synthesis of 1,7-diazaisoadamantane, 1,5-diazaisoadamantane and 1,6-diazahomobrendane

Three novel tricyclic diamines (1,7-diazaisoadamantane, 1,5-diazaisoadamantane, and 1,6-diazahomobrendane) were successfully synthesized using aromatic azaindoles and a flexible synthetic strategy.

Nucleophile‐Selective Cross‐Coupling Reactions with Vinyl and Alkynyl Bromides on a Dinucleophilic Aromatic Substrate

This study developed a nucleophile-selective cross-coupling reaction on an aromatic compound with two metal groups, enabling the use of vinyl and alkynyl bromides as electrophiles, offering a new tool for organic synthesis.

Palladium-catalyzed synthesis of 2,3-disubstituted 5-azaindoles via heteroannulation reaction and of 2-substituted 5-azaindoles through domino sila-Sonogashira/5-endo cyclization.

Palladium-catalyzed heteroannulation and sila-Sonogashira/5-endo cyclization efficiently synthesize diversely substituted 5-azaindoles in good yields.

Palladium-catalyzed asymmetric ring expansion of allenylcyclobutanols: an asymmetric Wagner-Meerwein shift.

This study developed a palladium-catalyzed asymmetric Wagner-Meerwein shift for efficient synthesis of functionalized cyclopentanones with alpha-chiral O-tertiary centers, offering excellent enantioselectivity and atom economy.

Discovery of an orally efficacious inhibitor of coagulation factor Xa which incorporates a neutral P1 ligand.

The most potent azaindole, 33 (RPR209685), is an orally efficacious inhibitor of coagulation factor Xa, selective against related serine proteases, and shows efficacy in the canine AV model of thrombosis.

Citations

Potential Safety Hazards Associated with Pd-Catalyzed Cross-Coupling Reactions

Pd-catalyzed cross-coupling reactions may pose underappreciated safety hazards due to their exothermic behavior, which is often overlooked by synthetic chemists.

Polyethyleneimine-Modified Polymer as an Efficient Palladium Scavenger and Effective Catalyst Support for a Functional Heterogeneous Palladium Catalyst

Polyethyleneimine-modified polymers effectively eliminate residual palladium species and serve as catalyst supports for chemoselective hydrogenation, with the TAm-supported catalyst showing better properties for chemoselective hydrogenation compared to the TAs-supported catalyst.