197706-51-7

Basic information

• Product Name: (2S)-6-fluoro-2-(oxiran-2-yl)chromane
• Synonyms: (2S)-6-Fluoro-2-(oxiran-2-yl)chromane; 2H-1-benzopyran, 6-fluoro-3,4-dihydro-2-oxiranyl-, (2S)-
• CAS NO: 197706-51-7
• Molecular Formula: C₁₁H₁₁FO₂
• Molecular Weight: 194.2
• EINECS: 606-374-7
• Mol File: 197706-51-7.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 291.7°C at 760 mmHg
• Flash Point: 137.8°C
• Density: 1.299g/cm³
• Vapor Pressure: 0.00334mmHg at 25°C
• Refractive Index: 1.568
• CAS DataBase Reference: (2S)-6-fluoro-2-(oxiran-2-yl)chromane(CAS DataBase Reference)
• NIST Chemistry Reference: (2S)-6-fluoro-2-(oxiran-2-yl)chromane(197706-51-7)
• EPA Substance Registry System: (2S)-6-fluoro-2-(oxiran-2-yl)chromane(197706-51-7)

Safety Data

• Hazardous Substances Data: 197706-51-7(Hazardous Substances Data)

Usage

Description

(2S)-6-fluoro-2-(oxiran-2-yl)chromane is an organic compound that serves as a crucial intermediate in the synthesis of pharmaceuticals, particularly Nebivolol, a β1-Adrenergic blocker. It is characterized by its unique molecular structure, which includes a fluorine atom and an oxirane ring, contributing to its reactivity and potential applications in the medical field.

Uses

Used in Pharmaceutical Industry:
(2S)-6-fluoro-2-(oxiran-2-yl)chromane is used as a key intermediate in the synthesis of Nebivolol, a β1-Adrenergic blocker. It plays a vital role in the development of this medication, which is utilized for the treatment of hypertension and heart failure. The compound's unique structure allows for the creation of Nebivolol, which helps regulate heart rate and blood pressure, providing relief from cardiovascular conditions.

Upstream product

• 1315508-96-3 (S)-2-chloro-1-((S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol 
• 1322623-11-9 1-(6-fluorochroman-2-yl)ethane-1,2-diol 
• 1219915-03-3 (S)-2-chloro-1-((R)-6-fluoro-1-benzopyran-2-yl)-ethanol 
• 303176-40-1 (R)-2-[(S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl-4-methylbenzenesulfonate 
• 793669-26-8 [1S*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 621-84-1 O-benzyl carbamate 

Downstream Products

• 303176-39-8 1-[6-fluoro-(2S)-3,4-dihydro-2H-benzopyran-2-yl]-(1R)-1,2-ethylene glycol 
• 1030385-16-0 (S)-2-benzylamino-1-((R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol 

Relevant articles and documents

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.

Method for preparing nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman

The invention discloses a method for preparing a nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman. The method includes the following steps that firstly, under the conditions that water, phosphate, inorganic alkali B1, zinc chloride, a hydrogen source, aldose reductase and NADPH exist, the temperature is 30-70 DEG C and the pH value is 6.0-8.0, a reduction reaction happens to 2-chloro-1-(6-fluorochromane-2-yl)-ethanon, and 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is obtained; secondly, 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is heated in a C1-C6 alkanol solvent and inorganic alkali B2 for a reflux reaction, an organic ester solvent is added dropwise for crystallization after the reaction ends, and 6-fluoro-2-epoxy ethyl chroman is obtained. The preparation method is mild in reaction condition, raw materials and solvents are easy to obtain, and the method is suitable for industrial production.

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.