35854-35-4

Upstream product

• 872-85-5 pyridine-4-carbaldehyde 
• 108-89-4 picoline 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 1879-16-9 1-methoxy-4-methylsulfanyl-benzene 
• 100-48-1 pyridine-4-carbonitrile 
• 100-09-4 4-methoxybenzoic acid 
• 2746-25-0 p-Methoxybenzyl bromide 
• 1934-93-6 6,7-dimethoxy-1-(4-methoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 110-86-1 pyridine 
• 70887-29-5 4-methoxybenzyl iodide 
• 31179-52-9 p-anisylmagnesium bromide 
• 63755-30-6 N-ethoxycarbonylpyridinium chloride 
• 80891-12-9 diisopropyl-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate 
• 882525-09-9 4-(diisopropoxy-phosphoryl)-4-[hydroxy-(4-methoxy-phenyl)-methyl]-4H-pyridine-1-carboxylic acid ethyl ester 

Downstream Products

• 66414-18-4 4-(pyridin-4-ylmethyl)phenol 
• 130407-11-3 4-(1-Methyl-1,2,3,6-tetrahydro-pyridin-4-ylmethyl)-phenol 
• 1242138-01-7 4,4-bis(4-methoxybenzyl)-1-(triisopropylsilyl)-1,4-dihydropyridine 
• 67916-76-1 4-(bis(4-methoxyphenyl)methyl)pyridine 
• 742051-67-8 6-(4-piperidinylmethyl)-2H-1,4-benzoxazin-3(4H)-one 
• 14548-47-1 (4-methoxyphenyl)(pyridin-4-yl)methanone 
• 420786-56-7 4-(4-methoxycarbonylmethoxy-3-nitro-benzyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 420786-32-9 4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 420786-66-9 4-(4-hydroxy-3-nitro-benzyl)-piperidine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Metal-Free Heterogeneous Semiconductor for Visible-Light Photocatalytic Decarboxylation of Carboxylic Acids

A suitable protocol for the photocatalytic decarboxylation of carboxylic acids was developed with metal-free ceramic boron carbon nitrides (BCN). With visible light irradiation, BCN oxidize carboxylic acids to give carbon-centered radicals, which were trapped by hydrogen atom donors or employed in the construction of the carbon-carbon bond. In this system, both (hetero)aromatic and aliphatic acids proceed the decarboxylation smoothly, and C-H, C-D, and C-C bonds are formed in moderate to high yields (35 examples, yield up to 93%). Control experiments support a radical process, and isotopic experiments show that methanol is employed as the hydrogen atom donor. Recycle tests and gram-scale reaction elucidate the practicability of the heterogeneous ceramic BCN photoredox system. It provides an alternative to homogeneous catalysts in the valuable carbon radical intermediates formation. Moreover, the metal-free system is also applicable to late-stage functionalization of anti-inflammatory drugs, such as naproxen and ibuprofen, which enrich the chemical toolbox.

Light-Induced Alkylation of (Hetero)aromatic Nitriles in a Transition-Metal-Free C-C-Bond Metathesis

A light-induced C-C-σ-bond metathesis was achieved through transition-metal-free activation of an unstrained C(sp3)-C(sp3)-σ-bond in 1-benzyl-1,2,3,4-tetrahydroisoquinolines. A photoredox-mediated single-electron oxidation of these precursor amines yield radical cations which undergo a homolytic cleavage of a C(sp3)-C(sp3)-σ-bond rather than the well-known α-C-H-scission. The resulting carbon-centered radicals are used in the ipso-substitution of (hetero)aromatic nitriles proceeding through another single-electron transfer-mediated C-C-bond cleavage and formation.

Synthesis of 4-benzylpyridines via Pd-catalyzed CH3-arylation of 4-picoline

A highly efficient synthesis of 4-benzylpyridines was developed via Pd-catalyzed C(sp3)-H arylation between 4-picoline and aryl halides. It was found that the best yields were achieved with a simple Pd(PPh3)4 catalyst and Cs2CO3 as the base. Compared with the known methods, our reaction does not require the use of a strong organometallic reagent as the base.

Palladium-Catalyzed Arylation of Benzylic C-H Bonds of Azaarylmethanes with Aryl Sulfides

Benzylic C-H arylation of azaarylmethanes with aryl sulfides has been developed by using a Pd-NHC catalyst and an amide base. Various azaarylmethanes and aryl sulfides were involved in the reaction to afford the corresponding diarylmethanes in good to excellent yields. Moreover, triarylmethane synthesis was accomplished through iterative arylations of 2- or 4-methylpyridine with two different aryl sulfides.

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.

Identification and development of an efficient route to SB-649915

The discovery and development of an efficient manufacturing route to the SSRI-5-HT1A receptor antagonist 6-[(1-{2-[(2-methyl-5-quinolinyl)oxy]ethyl}-4- piperidinyl)methyl]-2H-1,4-benzoxazin-3(4H)-one (SB-649915) 1 is described. The existing route to 1 involved coupling quinoline 6 with piperidine 5 and was considered lengthy as a consequence of the nine synthetic steps required to prepare 5. Two new routes to the key piperidine intermediate 5 are identified which deliver this compound in five and two steps respectively, from readily available materials using novel lithiation and Friedel-Crafts methodology respectively. The latter of these two routes was successfully demonstrated at 5 L scale to deliver 700 g of 5. Development to the methanesulfonate 34, an alternative to quinoline 6, is also described as is the final alkylation of piperidine 5 with this methanesulfonate 34 to deliver SB-649915 1.

Lewis acid promoted benzylic cross-couplings of pyridines with aryl bromides

Either ZnCl2, Sc(OTf)3, or BF3OEt 2 can promote the palladium-catalyzed arylation of methylpyridines and related heterocycles (see example). The complexation of the Lewis acid to the nitrogen atom in the heteroc

Synthesis of 5-substituted 7,8-benzomorphans by intramolecular cyclization of N-protected 4,4-disubstituted 1,4-dihydropyridines

An efficient and high yielding method for the synthesis of 7,8-benzomorphans with varying substituents at C5 has been developed. It is based on an acid-catalyzed intramolecular cyclization reaction of N-protected 4,4-disubstituted 1,4-dihydropyridines, wh

Regioselective synthesis of 4-alkylpyridines from pyridine and aldehydes via dipole reversal process of 1,4-dihydropyridine phosphonate

4-Alkylation of pyridine has been accomplished by the reaction of ylides, derivated from 1,4-dihydropyridine phosphonate via phosphonioalkoxycarbonylation of pyridine with aldehydes and subsequent elimination of diisopropyl phosphate followed by aromatization with potassium tert-butoxide.