303176-46-7

Basic information

• Product Name: (1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane
• Synonyms: (1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane;(1R)-1-[(2R)-6-Fluoro-3,4-dihydro-2H-1-benzopyran-2-yl]-1,2-ethanediol 2-(4-Methylbenzenesulfonate)
• CAS NO: 303176-46-7
• Molecular Formula: C₁₈H₁₉FO₅S
• Molecular Weight: 366.4038632
• Product Categories: Aromatics;Intermediates & Fine Chemicals. Sulfur & Selenium Compounds;Pharmaceuticals
• Mol File: 303176-46-7.mol

Chemical Properties

• Boiling Point: 540.4±50.0 °C(Predicted)
• Appearance: /
• Density: 1.340±0.06 g/cm3(Predicted)
• Solubility: Dichloromethane, Ethyl Acetate, Methanol
• PKA: 13.59±0.20(Predicted)
• CAS DataBase Reference: (1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane(CAS DataBase Reference)
• NIST Chemistry Reference: (1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane(303176-46-7)
• EPA Substance Registry System: (1’R,2R)-2-(2’-Tosyl-1’,2’-dihydroxyethyl)-6-fluorochromane(303176-46-7)

Safety Data

• Hazardous Substances Data: 303176-46-7(Hazardous Substances Data)

Usage

Chemical Properties

Pale Brown Solid

Uses

(+)-Nebivolol intermediates.

Upstream product

• 98-59-9 p-toluenesulfonyl chloride 
• 303176-45-6 1-[6-fluoro-(2R)-3,4-dihydro-2H-benzopyran-2-yl]-(1R)-1,2-ethylene glycol 
• 303176-44-5 2-(1,2-di(4-nitrophenylcarbonyloxy)-(1R)-ethyl)-6-fluoro-(2R)-3H,4H-chromene 
• 303176-36-5 ethyl 5-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-2-pentenoate 
• 303176-37-6 5-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-(E)-2-penten-1-ol 
• 303176-35-4 3-(2-tert-butyldimethylsilyloxy-5-fluoro-phenyl)-1-propanol 
• 783332-57-0 3-(2-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)propanal 
• 303176-34-3 2-alllyl-1-(tert-butyldimethylsilyloxy)-4-fluoro-benzene 
• 303176-43-4 1-[6-fluoro-(2R)-3,4-dihydro-2H-benzopyran-2-yl]-(1S)-1,2-ethylene glycol 
• 303176-38-7 5-(5-fluoro-2-hydroxy-phenyl)-E-2-penten-1-ol 
• 13997-72-3 1-allyl-2-hydroxy-5-fluorobenzene 
• 13990-72-2 1-allyloxy-4-fluorobenzene 
• 394-32-1 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one 
• 371-41-5 4-Fluorophenol 

Downstream Products

• 118457-14-0 (+)-Nebivolol 
• 1180001-17-5 d-(S,R,R,R)-benzyl nebivolol hydrochloride 
• 152520-56-4 DL-nebivolol hydrochloride 
• 1030385-17-1 (SRRR)-d-N-benzilnebivolol 
• 197706-50-6 6-fluoro-(2R)-2-[(2R)-2-oxiranyl]-3,4-dihydrobenzopyran 

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.

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 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.

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.

Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-Nebivolol

The total synthesis of (S,R,R,R)-Nebivolol, a hypertensive agent, is reported. Claisen rearrangement and a one-pot Sharpless asymmetric epoxidation, intramolecular epoxide opening with internal phenoxide anion to generate the chiral chromane are the key s