637763-71-4

Upstream product

• 74-90-8 hydrogen cyanide 
• 455-24-3 4-trifluoromethylbenzoic acid 
• 60-35-5 acetamide 
• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 64-17-5 ethanol 
• 3300-51-4 p-Trifluoromethylbenzylamine 
• 1694-31-1 tert-butyl acetoacetate 
• 1262155-48-5 C₂₀H₁₆F₃NO₃S 
• 75-36-5 acetyl chloride 
• 64-19-7 acetic acid 

Downstream Products

• 90389-04-1 Ethyl-(4-trifluoromethyl-benzyl)-amine; hydrochloride 
• 90390-12-8 N-[4-(trifluoromethyl)benzyl]ethanamine 

Relevant academic research and scientific papers

Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis

Recent years have witnessed important progress in synthetic strategies exploiting the reactivity of carbocations via photochemical or electrochemical methods. Yet, most of the developed methods are limited in their scope to certain stabilized positions in molecules. Herein, we report a metal-free system based on the iodine (I/III) catalytic manifold, which gives access to carbenium ion intermediates also on electronically disfavored benzylic positions. The unusually high reactivity of the system stems from a complexation of iodine (III) intermediates with BF3. The synthetic utility of our decarboxylative Ritter-type amination protocol has been demonstrated by the functionalization of benzylic as well as aliphatic carboxylic acids, including late-stage modification of different pharmaceutical molecules. Notably, the amination of ketoprofen was performed on a gram scale. Detailed mechanistic investigations by kinetic analysis and control experiments suggest two mechanistic pathways.

Hydrosilylative reduction of primary amides to primary amines catalyzed by a terminal [Ni-OH] complex

A terminal [Ni-OH] complex1, supported by triflamide-functionalized NHC ligands, catalyzes the hydrosilylative reduction of a range of primary amides into primary amines in good to excellent yields under base-free conditions with key functional group tolerance. Catalyst1is also effective for the reduction of a variety of tertiary and secondary amides. In contrast to literature reports, the reactivity of1towards amide reduction follows an inverse trend,i.e., 1° amide > 3° amide > 2° amide. The reaction does not follow a usual dehydration pathway.

Ruthenium-Catalyzed Reductive Amidation without an External Hydrogen Source

A catalytic reaction between aldehydes and primary amides that leads to N-alkylated amides was investigated. The developed protocol employs carbon monoxide as a deoxygenative agent and, therefore, avoids the use of an external hydrogen source. Cyclopentad

Direct Synthesis of Amides by Dehydrogenative Coupling of Amines with either Alcohols or Esters: Manganese Pincer Complex as Catalyst

The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable.

An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines

We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.

Dynamic path bifurcation in the Beckmann reaction: Support from kinetic analyses

The reactions of oximes to amides, known as the Beckmann rearrangement, may undergo fragmentation to form carbocations + nitriles when the migrating groups have reasonable stability as cations. The reactions of oxime sulfonates of 1-substituted-phenyl-2-propanone derivatives (7-X) and related substrates (8-X, 9a-X) in aqueous CH3CN gave both rearrangement products (amides) and fragmentation products (alcohols), the ratio of which depends on the system; the reactions of 7-X gave amides predominantly, whereas 9a-X yielded alcohols as the major product. The logk-logk plots between the systems gave excellent linear correlations with slopes of near unity. The results support the occurrence of path bifurcation after the rate-determining TS of the Beckmann rearrangement/fragmentation reaction, which has previously been proposed on the basis of molecular dynamics simulations. It was concluded that path-bifurcation phenomenon could be more common than thought and that a reactivity-selectivity argument based on the traditional TS theory may not always be applicable even to a well-known textbook organic reaction.

Benzyl amide-ketoacid inhibitors of HIV-integrase

Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. Previous reports have demonstrated that the diketoacid-based chemotype is a useful starting point for the design of inhibitors of this enzyme. In this study, one of the ketone groups is replaced by a benzylamide resulting in a new potent chemotype. A preliminary SAR study is carried out to investigate the substitution requirements on the phenyl ring and methylene group of the benzylamide.

ORTHO-SUBSTITUTED BENZOIC ACID DERIVATIVES FOR THE TREATMENT OF INSULIN RESISTANCE

The present invention provides a compound of formula (I), wherein n is 0, 1 or 2; R1 represents halo, a C1-4alkyl group which is optionally substituted by one or more fluoro, a C1-4alkoxy group which is optionally substitu