- 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.
- Devi, Runjun,Das, Sajal Kumar
-
-
Read Online
- 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
- -
-
Page/Page column 29-32
(2017/08/20)
-
- 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.
- -
-
Paragraph 0045
(2016/12/22)
-
- 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.
- -
-
Page/Page column 23
(2013/03/26)
-
- 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.
- -
-
Page/Page column 7
(2011/10/12)
-
- 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.
- -
-
Page/Page column 30
(2008/12/06)
-
- 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.
- -
-
Page/Page column 22
(2008/12/06)
-