5335-75-1

Usage

Synthesis Reference(s)

Tetrahedron Letters, 23, p. 3935, 1982 DOI: 10.1016/S0040-4039(00)87747-3

InChI:InChI=1/C9H13N/c1-2-3-4-9-5-7-10-8-6-9/h5-8H,2-4H2,1H3

Upstream product

• 110-86-1 pyridine 
• 543-63-5 n-butylmercuric chloride 
• 693-04-9 butyl magnesium bromide 
• 693-03-8 n-butyl magnesium bromide 
• 109-72-8 n-butyllithium 
• 84355-14-6 N-tert-butyldimethylsilylpyridinium triflate 
• 86801-34-5 4-Butyl-4H-pyridine-1-carboxylic acid phenyl ester 
• 100-43-6 4-vinylpyridine 
• 75-03-6 ethyl iodide 
• 626-61-9 4-Chloropyridine 
• 5799-73-5 acetaldehyde hydrazone 
• 113964-72-0 triphenyl(pyridin-4-yl)phosphonium trifluoromethanesulfonate 
• 42930-39-2 n-butylzinc chloride 

Downstream Products

• 24152-39-4 4-n-butylpiperidine 
• 38043-59-3 4-butyl-1,2,3,6-tetrahydro-pyridine 
• 388631-01-4 2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid benzyl ester 
• 31396-34-6 4-n-Butyl-pyridin-N-oxid 
• 372195-85-2 4-butylpiperidine hydrochloride 
• 317861-31-7 4-aminomethyl-N-[1-(4-butyl-pyridin-2-yl)-2-cyclohexyl-ethyl]-benzamide 
• 317861-29-3 5-Amino-pentanoic acid [(S)-1-(4-butyl-pyridin-2-yl)-2-cyclohexyl-ethyl]-amide 

Relevant academic research and scientific papers

Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketonesviaN2H4mediated deoxygenative couplings

Umpolung (polarity reversal) tactics of aldehydes/ketones have greatly broadened carbonyl chemistry by enabling transformations with electrophilic reagents and deoxygenative functionalizations. Herein, we report the first ruthenium-catalyzed β-selective alkylation of vinylpyridines with both naturally abundant aromatic and aliphatic aldehyde/ketonesviaN2H4mediated deoxygenative couplings. Compared with one-electron umpolung of carbonyls to alcohols, this two-electron umpolung strategy realized reductive deoxygenation targets, which were not only applicable to the regioselective alkylation of a broad range of 2/4-alkene substituted pyridines, but also amenable to challenging 3-vinyl and steric-embedded internal pyridines as well as their analogous heterocyclic structures.

Cobalt-Catalyzed Alkylation of Drug-Like Molecules and Pharmaceuticals Using Heterocyclic Phosphonium Salts

Alkylated pyridines are common in pharmaceuticals, and metal catalysis is frequently used to prepare this motif via Csp2-Csp3 coupling processes. We present a cobalt-catalyzed coupling reaction between pyridine phosphonium salts and alkylzinc reagents that can be applied to complex drug-like fragments and for late-stage functionalization of pharmaceuticals. The reaction generally proceeds at room temperature, and 4-position pyridine C-H bonds are the precursors in this strategy. Given the challenges in selectively installing (pseudo)halides in complex pyridines, this two-step process enables sets of molecules to be alkylated that would be challenging using traditional cross-coupling methods.

Manganese-Catalyzed Kumada Cross-Coupling Reactions of Aliphatic Grignard Reagents with N-Heterocyclic Chlorides

Herein we report the use of manganese(II) chloride for the catalytic generation of C(sp 2)-C(sp 3) bonds via Kumada cross-coupling. Rapid and selective formation of 2-alkylated N-heterocyclic complexes were observed in high yields with use of 3 mol% MnCl 2 THF 1.6 and under ambient reaction conditions (21 °C, 15 min to 20 h). Manganese-catalyzed cross-coupling is tolerant toward both electron-donating and electron-withdrawing functional groups in the 5-position of the pyridine ring, with the latter resulting in an increased reaction rate and a decrease in the amount of nucleophile required. The use of this biologically and environmentally benign metal salt as a catalyst for C-C bond formation highlights its potential as a catalyst for the late-stage functionalization of pharmaceutically active N-heterocyclic molecules (e.g., pyridine, pyrazine).

Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)

Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of thre

PYRIDINE SYNTHESIS VIA ANODIC OXIDATION OF 1-ACYLDIHYDROPYRIDINES

The preparation of several substituted pyridines via anodic oxidation of 1-acyldihydropyridines is reported

Alkylation of Pyridine in Free Radical Chain Reactions Utilizing Alkylmercurials

Pyridines or N,N,N',N'-tetramethyl-p-phenylenediamine will undergo a photostimulated free radical chain reaction with alkylmercury halides or carboxylates, yielding ring alkylated substitution products.Alkene mercuration products (R1CH(Y)CH(R2)HgX with Y=HO, RO, CH3CONH; X=Cl, CH3CO2, CF3CO2) can be used without isolation for the alkylation reaction

A Convenient Method for the Regioselective Synthesis of 4-Alkyl(aryl)pyridines Using Pyridinium Salts

RCu.BF3 reacted with 1-ethocycarbonylpyridinium chloride at the 4-position with almost complete regioselectivity (>99percent) to afford the corresponding 1,4-dihydropyridine derivatives in high yields (81-94percent).The dihydropyridines were oxidized by oxygen to give 4-alkyl(aryl)pyridines (38-68percent).Grignard reagents also reacted with 1-t-butyldimethylsilylpyridinium triflate with almost complete regioselectivity (>99percent) to afford the corresponding 1,4-dihydropyridines, which were easily oxidized to give 4-substituted pyridines in higher yields than above (58-70percent).

FACILE SYNTHESIS OF 4-SUBSTITUTED PYRIDINES USING GRIGNARD REAGENTS

N-t-Butyldimethylsilylpyridinium triflate (2) reacted with Grignard reagents at 4-position with almost complete regioselectivity (99percent) to afford the corresponding 1,4-dihydropyridine derivatives (3), which are easily oxidized by oxygen to give 4-substituted pyridines (4: 58-70percent).

Regioselective Addition of Grignard Reagents to 1-Acylpyridinium Salts. A Convenient Method for the Synthesis of 4-Alkyl(aryl)pyridines

The addition of Grignard reagents to 1-acylpyridinium salts afforded 1-acyl-2-alkyl(aryl)-1,2-dihydropyridines and 1-acyl-4-alkyl(aryl)-1,4-dihydropyridines.The regioselectivity of this reaction, 1,2- vs. 1,4-addition, was examined and found to be dependent upon the structures of the Grignard reagent and the 1-acyl group.Pyridine, 2-picoline, and 3-picoline were studied, and in most cases, significant amounts of 1,4-addition occurred.When a catalytic amount of cuprous iodide was present, nearly exclusive 1,4-addition resulted.The crude 1,4-dihydropyridines were aromatized by heating with sulfur to provide 4-substituted pyridines and picolines in good yield and high isomeric purity.