Synthesis of 3-Quinuclidinol by the Cyclodehydration of (4-Piperidyl)-1,2-ethanediol

Aaron, Herbert S.; Owens, Omer O.; Rosenstock, Paul; Leonard, Stanley; Elkin, Samuel; Miller, Jacob I.

doi:10.1021/jo01015a561

Cited by 9 publications

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“…Chromatography over a 20 ft X 0.375 in. 20% Silicone rubber on 60-80 Chromosorb W column (column temperature 150°, He flow 30 cc min-1) separated the larger component, bp 69-70°(0.2 mm), which was identical with the known 1-benzyl-I, 2,5,6-tetrahydropyridine (14) [lit.16 bp 68°( 0.1 mm); 96°( 5 mm)]; uv max (95% EtOH) 251 µ (e 300), 257 (335), and 263 (332); nmr (CDC13) 7.23 (s, 5, aromatic), 5.73-5.50 (m, 2, CH), 3.54 (s, 2, -CH2C6H5), 3.03-2.80 (m, 2, C-2 methylene), 2.68-2.41 (m, 2, C-6 methylene), and 2.36-2.00 (m, 2, C-5 methylene).…”

mentioning

confidence: 75%

Azabicyclic alcohols. VI. Azabicyclo [2.2.1]heptan-3-ol epimers

Spry¹,

Aaron²

1969

J. Org. Chem.

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confidence: 75%

Azabicyclic alcohols. VI. Azabicyclo [2.2.1]heptan-3-ol epimers

Spry¹,

Aaron²

1969

J. Org. Chem.

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“…“Cyclodehydration” by thermolysis was also used in the synthesis of quinuclidinol ( 52 ). Dihydroxylation of 4-vinylstyrene ( 50 ), pyridinium salt formation and catalytic hydrogenation gave the 4-(dihydroxyethyl)-piperidine ( 51 ) which was cyclised as before [ 85 ]. Although this sequence is brief it suffers from two poor steps.…”

Section: Muscarinic Agonistsmentioning

confidence: 99%

Muscarinic Receptor Agonists and Antagonists

2001

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A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes). Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

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The hydroxyacetylpiperidines and their N‐benzyl derivatives. The 2‐hydroxymethyl‐2‐piperidyl‐ and 2‐hydroxymethyl‐2‐pyridyl‐1,3‐dioxolanes

Nielsen

Platt

1969

Journal of Heterocyclic Chem

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The hydroxyacetylpiperidines, their ethylene ketals, and the N‐benzyl derivatives of these new piperidines have been synthesized. Methylolation of 2‐(2‐ and 4‐pyridyl)‐1,3‐dioxolanes by heating with paraformaldehyde at 185° led to 2‐hydroxymethyl‐2‐(2‐ and 4‐pyridyl)‐i,3‐dioxolanes (7,8, respectively). 2‐Hydroxymethyl‐2‐(3‐pyridyl)‐1,3‐dioxolane (13) was obtained by reaction of 2‐bromomethyl‐2‐(3‐pyridyl)‐1,3‐dioxolane with aqueous sodium hydroxide at 190°. Hydrogenation of these pyridine ketals with rhodium‐charcoal catalyst produced the corresponding piperidine ketals (16,17,18). Acid hydrolysis of the piperidine ketals and their N‐benzyl derivatives led to the hydroxyacetylpiperidines (1,2,3) and their N‐benzyl derivatives (25,26,27). The N‐benzylhydroxyacetylpiperidines undergo rapid hydrogenolysis with palladium‐charcoal catalyst to produce the hydroxyacetylpiperidines. Further hydrogenation produces the piperidyl‐1,2‐ethanediols. The hydroxyacetylpiperidines are somewhat unstable, hygroscopic substances which polymerize with dehydration on standing; in solution they are relatively stable. Their N‐benzyl, ketal, and hydrochloride salt derivatives, on the other hand, represent stable, synthetically useful intermediates from which the reactive trifunctional hydroxyacetylpiperidines may readily be prepared.

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Synthesis of 3-Quinuclidinol by the Cyclodehydration of (4-Piperidyl)-1,2-ethanediol

Cited by 9 publications

References 0 publications

Azabicyclic alcohols. VI. Azabicyclo [2.2.1]heptan-3-ol epimers

Azabicyclic alcohols. VI. Azabicyclo [2.2.1]heptan-3-ol epimers

Muscarinic Receptor Agonists and Antagonists

The hydroxyacetylpiperidines and their N‐benzyl derivatives. The 2‐hydroxymethyl‐2‐piperidyl‐ and 2‐hydroxymethyl‐2‐pyridyl‐1,3‐dioxolanes

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