134362-34-8

Usage

Uses

Used in Pharmaceutical Industry:
(S)-2-TERT-BUTOXYCARBONYLAMINO-3-(4-FLUORO-PHENYL)-PROPIONIC ACID METHYL ESTER is used as a building block for the synthesis of pharmaceutical compounds due to its potential analgesic and anti-inflammatory properties.
Used in Pain Management:
As a selective COX-2 inhibitor, (S)-2-TERT-BUTOXYCARBONYLAMINO-3-(4-FLUORO-PHENYL)-PROPIONIC ACID METHYL ESTER is used for the development of drugs aimed at managing pain by reducing inflammation and pain without affecting the stomach lining.
Used in Inflammatory Condition Treatment:
(S)-2-TERT-BUTOXYCARBONYLAMINO-3-(4-FLUORO-PHENYL)-PROPIONIC ACID METHYL ESTER is also utilized in the development of drugs for treating inflammatory conditions, capitalizing on its selective COX-2 inhibition to target the inflammatory response effectively.

Upstream product

• 352-34-1 4-fluoro-1-iodobenzene 
• 93267-04-0 N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 55477-80-0 methyl 2-[(tert-butoxycarbonyl)amino]acrylate 
• 151842-29-4 N-tert-butoxycarbonyl-4-(tri-n-butylstannyl)-L-phenylalanine methyl ester 
• 41153-30-4 Boc-Phe(p-F) 
• 74-88-4 methyl iodide 
• 175844-11-8 methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-bromopropionate 
• 69942-12-7 N-tert-butoxycarbonylserine methyl ester 
• 1765-93-1 4-fluoroboronic acid 
• 67-56-1 methanol 

Downstream Products

• 1187648-02-7 (S)-tert-butyl 4-(diethoxyphosphoryl)-1-(4-fluorophenyl)-3-oxobutan-2-ylcarbamate 
• 1240613-20-0 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate 
• 1240613-21-1 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-fluoro-3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate 

Relevant academic research and scientific papers

Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis

We describe herein a two-step process for the conversion of serine to a wide array of optically pure unnatural amino acids. This method utilizes a photocatalytic cross-electrophile coupling between a bromoalkyl intermediate and a diverse set of aryl halides to produce artificial analogues of phenylalanine, tryptophan, and histidine. The reaction is tolerant of a broad range of functionalities and can be leveraged toward the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.

Site- and Stereoselective Chemical Editing of Thiostrepton by Rh-Catalyzed Conjugate Arylation: New Analogues and Collateral Enantioselective Synthesis of Amino Acids

The synthesis of complex, biologically active molecules by catalyst-controlled, selective functionalization of complex molecules is an emerging capability. We describe the application of Rh-catalyzed conjugate arylation to the modification of thiostrepton, a complex molecule with potent antibacterial properties for which few analogues are known. By this approach, we achieve the site- and stereoselective functionalization of one subterminal dehydroalanine residue (Dha16) present in thiostrepton. The broad scope of this method enabled the preparation and isolation of 24 new analogues of thiostrepton, the biological testing of which revealed that the antimicrobial activity of thiostrepton tolerates the alteration of Dha16 to a range of amino acids. Further analysis of this Rh-catalyzed process revealed that use of sodium or potassium salts was crucial for achieving high stereoselectivity. The catalyst system was studied further by application to the synthesis of amino esters and amides from dehydroalanine monomers, a process which was found to occur with up to 93:7 er under conditions milder than those previously reported for analogous reactions. Furthermore, the addition of the same sodium and potassium salts as applied in the case of thiostrepton leads to a nearly full reversal of the enantioselectivity of the reaction. As such, this study of site-selective catalysis in a complex molecular setting also delivered synergistic insights in the arena of enantioselective catalysis. In addition, these studies greatly expand the number of known thiostrepton analogues obtained by any method and reveal a high level of functional group tolerance for metal-catalyzed, site-selective modifications of highly complex natural products.

Evidence for the role of tetramethylethylenediamine in aqueous negishi cross-coupling: Synthesis of nonproteinogenic phenylalanine derivatives on water

The structure of the alkylzinc-tetramethylethylenediamine (TMEDA) cluster cation 3 has been determined in the gas phase by a combination of tandem mass spectrometry, infrared multiphoton dissociation (IRMPD) spectroscopy, and DFT calculations. Both sets of experimental results establish the existence of a strongly stabilizing interaction of TMEDA with the zinc cation. High-level DFT calculations on the alkylzinc-TMEDA cluster cation 3 allowed the identification of two low energy conformers, each featuring a four-coordinate zinc atom with a bidentate TMEDA ligand, and internal coordination from the carbonyl group of the Boc group to zinc. The experimental IRMPD spectrum is reproduced with an appropriately weighted combination of the IR spectra of the two conformers identified by theory. DFT calculations on the structure of the alkylzinc halide 2 with coordinated TMEDA using the PCM model of water solvent suggest that TMEDA can promote ionization of the zinc-iodine bond in organozinc iodides under aqueous conditions, providing a credible explanation for the role of TMEDA in stabilizing the carbon-zinc bond. Reaction of the serine-derived iodide 1 with aryl iodides "on water", promoted by nano zinc in the presence of PdCl2 (Amphos) 2 (5 mol %) and TMEDA, leads to the formation of protected phenylalanine derivatives 4 in reasonable yields. In the case of ortho-substituted aryl iodides and aryl iodides that are solids at room temperature, conducting the reaction at 65°C gives improved results. In all cases, the product 5 of reductive dimerization of the iodide 1 is also isolated.

Much improved conditions for the Negishi cross-coupling of iodoalanine derived zinc reagents with aryl halides

(Chemical Equation Presented) A combination of Pd2(dba) 3 and SPhos (1:2 molar ratio) is an excellent precatalyst for the Negishi cross-coupling of the serine-derived organozinc reagent 2 with aryl halides, including previously difficult ortho-substituted examples. In the case of meta- and para-substituted aryl halides, Pd-loadings of 0.5 mol % give satisfactory results. Use of 2-iodoaniline as substrate gives the lactam 12 in good yield. 2009 American Chemical Society.

Functionalization of aromatic amino acids via direct C-H activation: Generation of versatile building blocks for accessing novel peptide space

Functionalized α-amino acid building blocks have been prepared in good yield with high regiocontrol and preservation of stereochemistry via iridium-catalyzed borylation of suitably protected aromatic α-amino acid derivatives. The utility of these systems

FLUORINATION OF ORGANIC COMPOUNDS

Methods for fluorinating organic compounds are described herein.

Silver-catalyzed late-stage fluorination

Carbon-fluorine bond formation by transition metal catalysis is difficult, and only a few methods for the synthesis of aryl fluorides have been developed. All reported transition-metal-catalyzed fluorination reactions for the synthesis of functionalized arenes are based on palladium. Here we present silver catalysis for carbon-fluorine bond formation. Our report is the first example of the use of the transition metal silver to form carbon-heteroatom bonds by cross-coupling catalysis. The functional group tolerance and substrate scope presented here have not been demonstrated for any other fluorination reaction to date.

PYRIDAZINE DERIVATIVES AS FACTOR XIA INHIBITORS

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein the variables A, L1, L2, R2, R11, and M are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Access to enantioenriched α-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation

Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected α-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the α carbon explaining the high levels of enantioselectivity attained in controlling this α chiral center.

Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides

The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)2 or Pd2(dba)3 in combination with P(o-Tol)3 as catalyst in DMF at 50 °C. Similar results are obtained using Pd[PtBu3]2 as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.