129050-23-3

Usage

Chemical Properties

Pale Yellow Oil

Uses

(-)-Nebivolol intermediate.

InChI:InChI=1/C11H11FO2/c12-8-2-4-9-7(5-8)1-3-10(14-9)11-6-13-11/h2,4-5,10-11H,1,3,6H2/t10-,11?/m0/s1

Upstream product

• 793669-26-8 [1R*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 99199-90-3 6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran 
• 100-46-9 benzylamine 
• 1322623-11-9 1-(6-fluorochroman-2-yl)ethane-1,2-diol 
• 1219915-05-5 (S)-6-fluoro-2-(oxiran-2-yl)chroman 
• 1219915-03-3 (S)-2-chloro-1-((R)-6-fluoro-1-benzopyran-2-yl)-ethanol 
• 621-84-1 O-benzyl carbamate 
• 905454-58-2 (S,S)-(+)-α-[(p-toluenesulfonyloxy)methyl](6-fluoro-2-chromanyl)methanol 

Downstream Products

• 118457-16-2 nebivolol 
• 1199945-26-0 2-{benzyl-[2-(6-fluoro-chroman-2-yl)-2-hydroxy-ethyl]-amino}-1-(6-fluoro-chroman-2-yl)-ethanol 
• 152520-56-4 DL-nebivolol hydrochloride 

Relevant academic research and scientific papers

PROCESS FOR THE SYNTHESIS OF INTERMEDIATES OF NEBIVOLOL

The present invention relates to a novel process for the synthesis of the intermediate compounds constituted by chromanyl haloketones of formula III and 6-fluoro-2-(oxiran-2-yl) chromans of formula I. The intermediates thus obtained can be used for the sy

PROCESS FOR THE PREPARATION OF EPOXIDES AS INTERMEDIATES FOR THE SYNTHESIS OF NEBIVOLOL

The present invention relates to a novel process of synthesis of epoxides, 6-fluoro-2- (oxiran-2-yl) chroman (Figure 1), intermediates for the synthesis of nebivolol, depicted in Scheme (1), enabling to obtain the above- mentioned epoxides in a racemic or semichiral form.

PROCESS FOR THE PREPARATION OF NEBIVOLOL

The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.

METHOD FOR PREPARING NEBIVOLOL

The present invention relates to a process for the preparation of nebivolol and, more particularly, to an improved process of synthesizing an alpha-haloketone of formula a key intermediate in the preparation of nebivolol.

PROCESS FOR PREPARING NEBIVOLOL

The present invention relates to a process for preparing Nebivolol and, more particularly, to an improved process for synthesizing enantiomerically enriched 6-fluoro chroman alcohol or epoxide derivatives of formula, wherein R and X is defined in the description; as useful intermediates in the preparation of Nebivolol.

Asymmetric-catalysed preparation and stereochemistry of (R,R)-,(S,R)-(6-fluoro-2-chromanyl)-1,2-ethanediol

(R,R)-,(S,R)-1-(6-fluoro-2-chromanyl)-1,2-ethanediol 1a/1b were prepared by hydrolytic kinetic resolution (HKR) of terminal racemic epoxides using (R,R)-SalenCo(OAc) as a catalyst. Their configurations were established by comparison with two authentic samples by HPLC.

Hydroxylated nebivolol metabolites

Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.