303176-45-6

Basic information

• Product Name: (1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane
• Synonyms: (1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane;(1R)-1-[(2R)-6-Fluoro-3,4-dihydro-2H-1-benzopyran-2-yl]-1,2-ethanediol
• CAS NO: 303176-45-6
• Molecular Formula: C₁₁H₁₃FO₃
• Molecular Weight: 212.2175232
• Product Categories: Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 303176-45-6.mol

Chemical Properties

• Melting Point: 92-94 °C
• Boiling Point: 384.8°C at 760 mmHg
• Flash Point: 175.6°C
• Appearance: /
• Density: 1.308g/cm³
• Vapor Pressure: 1.31E-06mmHg at 25°C
• Refractive Index: 1.558
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly, Heated), Methanol (Slightly)
• PKA: 14.25±0.20(Predicted)
• CAS DataBase Reference: (1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane(CAS DataBase Reference)
• NIST Chemistry Reference: (1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane(303176-45-6)
• EPA Substance Registry System: (1’R,2R)-2-(1’,2’-Dihydroxyethyl)-6-fluorochromane(303176-45-6)

Safety Data

• Hazardous Substances Data: 303176-45-6(Hazardous Substances Data)

Usage

Uses

(+)-Nebivolol intermediate.

InChI:InChI=1/C11H13FO3/c12-8-2-4-10-7(5-8)1-3-11(15-10)9(14)6-13/h2,4-5,9,11,13-14H,1,3,6H2/t9-,11-/m1/s1

Upstream product

• 371-41-5 4-Fluorophenol 
• 394-32-1 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one 
• 13990-72-2 1-allyloxy-4-fluorobenzene 
• 13997-72-3 1-allyl-2-hydroxy-5-fluorobenzene 
• 303176-38-7 5-(5-fluoro-2-hydroxy-phenyl)-E-2-penten-1-ol 
• 303176-34-3 2-alllyl-1-(tert-butyldimethylsilyloxy)-4-fluoro-benzene 
• 783332-57-0 3-(2-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)propanal 
• 303176-35-4 3-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-1-propanol 
• 303176-37-6 5-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-(E)-2-penten-1-ol 
• 303176-36-5 ethyl 5-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-2-pentenoate 
• 793669-26-8 [1R*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 1030385-08-0 (R)-6-fluoro-3,4-dihydro-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2H-chromene 
• 1030385-06-8 6-fluoro-3,4-dihydro-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2H-chromene 
• 197706-48-2 (2R)-6-fluoro-2-vinylchroman 

Downstream Products

• 118457-14-0 (+)-Nebivolol 
• 197706-50-6 6-fluoro-(2R)-2-[(2R)-2-oxiranyl]-3,4-dihydrobenzopyran 
• 303176-46-7 (R)-2-[(R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl-4-methylbenzenesulfonate 

Relevant articles and documents

Synthesis of intermediate compound and [...] (by machine translation)

Synthesis of intermediate compounds [a] and [...]. [Solution] a [...], asymmetric epoxidation, sulfonyl halide in the presence of base catalyst by sulfonation, alkylation of amines, such as synthesized by a series of cross-coupling reaction. [Effect] [...] important from the viewpoint of pharmacological value, high efficiency, low cost, and which meets the requirements of industrial, optical isomers may be prepared [...] and develop a method, which is very economical in social benefit. [Drawing] no (by machine translation)

NEBIVOLOL SYNTHESIS METHOD AND INTERMEDIATE COMPOUND THEREOF

The present invention relates to nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof, and a method for preparing the intermediate compound.

Nebivolol synthetic method and intermediate compounds of the

The present invention relates to a synthesis method and an intermediate compound of nebivolol. Specifically the invention relates to the method for synthesizing the nebivolol, the intermediate compound of the nebivolol, and a method for preparing the intermediate compound.

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

While the exploitation of the Sharpless asymmetric dihydroxylation as the source of chirality in the synthesis of acyclic molecules and saturated heterocycles has been tremendous, its synthetic utility toward chiral benzo-annulated heterocycles is relatively limited. Thus, in the search for wider applications of Sharpless asymmetric dihydroxylation-derived diols for the synthesis of benzo-annulated heterocycles, we report herein our studies in the asymmetric synthesis of (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as late-stage intermediates for the asymmetric synthesis of the antihypertensive drug (S,R,R,R)-nebivolol. Noteworthy is that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose.

A process for the preparation of nebivolol and wherein the intermediate compound

The invention discloses a preparation method of nebivolol used for preparing medicines for treating hypertension of slight or medium degrees, and an intermediate compound. The preparation method comprises the following steps: taking 6-fluoro-2-(1-hydroxy-2-paratoluensulfonyl oxygroup-ethyl)-3,4-dihydrobenzopyrans as an initial raw material, introducing amino, then coupling with 6- fluoro-3,4-dihydro-2-epoxy ethyl-2H-1-benzopyran, and preparing (S,R,R,R) and (R,S,S,S)-nebivolol. Compared with a prior art, the preparation method has the advantages of novel design, simple operation and high yield, the usage of hazardous reagent such as ssodium azide and sodium hydride can be avoided, a column chromatography purifying method is avoided, so that the preparation method conforms to industrial production.

Sulfoxide-directed stereocontrolled access to 2H-chromans: Total synthesis of the (S,R,R,R)-enantiomer of the antihypertensive drug nebivolol

A homochiral sulfoxide-directed reductive deoxygenation of 2-(p-tolylsulfinyl)methyl-2-chromanols allows the stereoselective formation of 2H-chromans with up to 95:5 diastereoisomeric ratio. This new methodology was applied in a short and convergent enantioselective synthesis of the (S,R,R,R)-enantiomer of the antihypertensive drug Nebivolol. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

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.

PROCESS FOR PREPARING NEBIVOLOL

The present invention relates to a process for preparing nebivolol and, more particularly, to a process for preparing d-nebivolol and its enantiomer /-nebivolol or acid addition salts thereof starting from commercially available or easily obtainable 2,2-dimethyl-l,3 dioxolane-4- carbaldehyde and a vinyl Grignard reagent.

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.

Synthesis of (S,R,R,R)-α,α′-iminobis(methylene)bis(6- fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol)

The β1-adrenergic antagonist (S,R,R,R)-α, α′-iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2- methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed. Georg Thieme Verlag Stuttgart.