348626-43-7

Basic information

• Product Name: benzyl 4-morpholinophenylcarbamate
• Synonyms: benzyl 4-morpholinophenylcarbamate
• CAS NO: 348626-43-7
• Molecular Weight: 312.368
• Mol File: 348626-43-7.mol

Chemical Properties

• CAS DataBase Reference: benzyl 4-morpholinophenylcarbamate(CAS DataBase Reference)
• NIST Chemistry Reference: benzyl 4-morpholinophenylcarbamate(348626-43-7)
• EPA Substance Registry System: benzyl 4-morpholinophenylcarbamate(348626-43-7)

Safety Data

• Hazardous Substances Data: 348626-43-7(Hazardous Substances Data)

Upstream product

• 2524-67-6 4-morpholino-4-yl-phenylamine 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 264601-17-4 (R)-3-(4'-N-morpholinophenyl)-5-(hydroxymethyl)-oxazolidin-2-one 
• 438056-69-0 4-(4-aminophenyl)morpholin-3-one 
• 1313613-18-1 [4-(3-oxo-morpholin-4-yl)phenyl]carbamic acid benzyl ester 
• 952288-54-9 (S)-5-Aminomethyl-3-(4-morpholin-4-yl-phenyl)-oxazolidin-2-one 

Relevant articles and documents

Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4- (3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): An oral, direct factor Xa inhibitor

Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.

Preparation method of Rivaroxaban intermediates

The invention discloses a preparation method of Rivaroxaban intermediates. The invention relates to a green and efficient preparation method of 4-(4-aminophenyl)morpholinyl-3-one and an amino protected derivative thereof. A structure of a formula II is obtained through an oxidation reaction of a structure of a formula II, and a structure of a formula I can be obtained through a deprotection reaction of the structure of the formula II, wherein the compound I and the compound II are both important intermediates for synthesizing the anticoagulation drug Rivaroxaban. Potassium permanganate is usedas an oxidizing agent in the oxidation reaction, tetraethyl benzyl ammonium chloride (TEBAC) is used as a phase transfer catalyst, dichloromethane is used as a solvent, and the reaction temperature in the oxidation reaction is 15-55 DEG C. The invention provides the preparation method of the Rivaroxaban intermediates, and the preparation method has the advantages that the raw materials are cheapand easily available, the reactions are mild in condition and are easy to operate, the preparation method is green and is friendly to the environment, the intermediate products and the final product are easy to purify, the total yield is high, industrial production is easy to realize, and the preparation method is effective and practical.

An exploratory and mechanistic study of the defluorination of an (aminofluorophenyl)oxazolidinone: SN1(Ar*) vs. S R+N1(Ar*) mechanism

The morpholinofluorophenyloxazolidinone 1 (the antibacterial drug linezolid) is found to undergo reductive defluorination upon irradiation in water (Φ 0.33), in some of the products accompanied by the simultaneous oxidative degradation of the morpholine side chain. In the presence of chloride, iodide and pyrrole, the fluorine is substituted by these groups (with pyrrole, in position 2). The defluorination is less efficient in methanol and mainly leads to reduction (Φ 0.053). These data can be accommodated through two different mechanisms, viz. either C-F bond heterolysis to give a phenyl cation [SN1(Ar*)], or ionization to give a radical cation [S R+N1(Ar*)]. Steady-state and time resolved data have been gathered for clarifying this issue. It is found that, indeed, ionization of 1 is efficient and proceeds from the singlet, but leads to no irreversible change. On the contrary, triplet 31 (lifetime 0.5 μs in MeOH, 0.1 μs in water) fragments and gives the corresponding triplet phenyl cation. The last intermediate explains well the observed hydrogen abstraction both inter- (from the solvent, when this is reducing) and intramolecularly (from the morpholine group), as well as addition to a charged anion or to a neutral π nucleophile such as pyrrole. The rationalization is supported by the study of some related molecules. Thus, the only photochemical reaction from the non fluorinated analogue of linezolid (that ionizes just as 1) is an inefficient degradation of the morpholine chain (Φ 0.001), while a simple model such as N-(2-fluorophenyl)morpholine undergoes photosolvolysis in water and is not trapped by pyrrole.

ISOLATED DESFLUORO-LINEZOLID, PREPARATION THEREOF AND ITS USE AS A REFERENCE MARKER AND STANDARD

The present invention provides an isolated linezolid impurity, desfluoro linezolid, the preparation thereof and its use as a reference standard.