- Amino alcohols using the optically active amino alcohol derivative bi- Nord complex boron - -
-
Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enationselective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield.
- -
-
Paragraph 0064; 0071-0076; 0281-0283; 0285-0286
(2021/04/16)
-
- Bisguanidinium-Catalyzed Epoxidation of Allylic and Homoallylic Amines under Phase Transfer Conditions
-
A highly enantioselective epoxidation reaction of allylic and homoallylic amines has been disclosed using an ion pair catalyst, which consists of chiral cationic bisguanidinium [BG]2+ and an achiral tetraperoxyditungstate anion [W2O2(μ-O)(O2)4]2-. The terminal oxidant is a stoichiometric amount of aqueous hydrogen peroxide, an environmentally benign reagent. Up to 96% enantiomeric excess and 99% yields were achieved for 1,1′-disubstituted and 1,2-disubstituted allylic protected amines and 1,2-disubstituted homoallylic protected amines. The identity of the ion pair catalyst was uncovered using X-ray crystallography and revealed that the achiral tetraperoxyditungstate anion species [W2O2(μ-O)(O2)4]2- is nudged nicely into the central cavity of the chiral dication. The ion pair catalyst was also characterized using infrared (IR) and Raman spectroscopies. The synthesis of (-)-venlafaxine was achieved via this reported methodology to demonstrate its usefulness.
- Chin, Kek Foo,Kabylda, Adil M.,Lee, Richmond,Leow, Dasheng,Li, Yongxin,Tan, Choon-Hong,Xia Ang, Esther Cai,Ye, Xinyi,Zhang, Xin
-
p. 2684 - 2691
(2020/03/11)
-
- Enantioseparation of chiral pharmaceuticals by vancomycin-bonded stationary phase and analysis of chiral recognition mechanism
-
The drug chirality is attracting increasing attention because of different biological activities, metabolic pathways, and toxicities of chiral enantiomers. The chiral separation has been a great challenge. Optimized high-performance liquid chromatography (HPLC) methods based on vancomycin chiral stationary phase (CSP) were developed for the enantioseparation of propranolol, atenolol, metoprolol, venlafaxine, fluoxetine, and amlodipine. The retention and enantioseparation properties of these analytes were investigated in the variety of mobile phase additives, flow rate, and column temperature. As a result, the optimal chromatographic condition was achieved using methanol as a main mobile phase with triethylamine (TEA) and glacial acetic acid (HOAc) added as modifiers in a volume ratio of 0.01% at a flow rate of 0.3?mL/minute and at a column temperature of 5°C. The thermodynamic parameters (eg, ΔH, ΔΔH, and ΔΔS) from linear van 't Hoff plots revealed that the retention of investigated pharmaceuticals on vancomycin CSP was an exothermic process. The nonlinear behavior of lnk′ against 1/T for propranolol, atenolol, and metoprolol suggested the presence of multiple binding mechanisms for these analytes on CSP with variation of temperature. The simulated interaction processes between vancomycin and pharmaceutical enantiomers using molecular docking technique and binding energy calculations indicated that the calculated magnitudes of steady combination energy (ΔG) coincided with experimental elution order for most of these enantiomers.
- Li, Jiaxi,Liu, Ruixia,Wang, Liyang,Liu, Xiaoling,Gao, Hongjie
-
p. 236 - 247
(2019/02/01)
-
- Efficient resolution of venlafaxine and mechanism study via X-ray crystallography
-
Numbers of resolving factors were investigated to improve resolution of venlafaxine 1. An effective resolving agent, O,O′-di-p-toluoyl-(R, R)-tartaric acid 2, was screened using similar method of ‘Dutch resolution’ from tartaric acid derivatives. The resolution efficiency was up to 88.4%, when the ratio of rac-1 and 2 was 1:0.8 in THF with little water (10:1?v/v). Enantiomerically pure venlafaxine was prepared with 99.1% ee in 82.2% yield. The chiral resolution mechanism was first explained through X-ray crystallographic study. One diastereomeric salt with well solubility forms a columnar supramolecular structure as the acidic salt (R)-1·2, while the other diastereomeric salt with less solubility forms a multilayered sandwich supramolecular structure by enantio-differentiation self-assembly as the neutral salt 2(S)-1·2. The water molecules play a key role in the optical resolution, as indicated by the special structures of the diastereomeric salts.
- Liu, Zhi-Jin,Liu, Han,Chen, Xuan-Wen,Lin, Min,Hu, Yu,Tuo, Xun,Yuan, Zhong-Yi,Sun, Xiao-Xia
-
p. 268 - 274
(2018/02/19)
-
- Application of Unusual Grignard Reaction for the Stereoselective Synthesis of Antidepressant Drug (R)-(-)-Venlafaxine
-
An enantioselective synthesis of antidepressant drug (R)-(-)-venlafaxine is accomplished as an application of recently explored unusual Grignard reaction. An innovative method for the generation of chirality at extremely reactive benzylic center along with determination of absolute stereochemistry has been discussed. The key steps involved in the synthesis include Sharpless asymmetric dihydroxylation for the induction of chirality and an unusual Grignard reaction.
- Chavan, Subhash P.,Khatod, Harshali S.
-
p. 1410 - 1418
(2017/03/11)
-
- NOVEL PROCESS FOR TOTAL SYNTHESIS OF VENLAFAXINE
-
There is a need for short, resolution free asymmetric process for synthesis of one isomer of venlafaxine, (-)-venlafaxine. The invention provides a novel, short process of synthesis of (-)-venlafaxine, with yield greater than 50% and ee> 99%. This process can be used for racemic synthesis of venlafaxine with overall yield 65%.
- -
-
-
- DERIVATIVES OF (-)-VENLAFAXINE AND METHODS OF PREPARING AND USING THE SAME
-
Methods of preparing, and compositions comprising, derivatives of (?)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
- -
-
Paragraph 0091
(2015/11/23)
-
- ASYMMETRIC SYNTHESIS OF (-)-VENLAFAXINE USING ORGANOCATALYST
-
The patent discloses an asymmetric synthesis of (?)-venlafaxine using an organocatalyst via a unified strategy employing organcatalytic Michael addition, regio-selective dehydration and selective epoxide ring opening.
- -
-
-
- A protecting group free and scalable approach towards total synthesis of (-)-venlafaxine
-
A protecting group free asymmetric total synthesis of (-)-venlafaxine is reported. The strategy employs Sharpless epoxidation and regio-selective epoxide ring opening by an in situ generated Gilman reagent as key steps. This paper reports a 53% overall yield in 6 steps for total synthesis of (-)-venlafaxine. This journal is the Partner Organisations 2014.
- Chavan, Subhash P.,Pawar, Kailash P.,Garai, Sumanta
-
p. 14468 - 14470
(2014/04/17)
-
- ASYMMETRIC SYNTHESIS OF (-)-VENLAFAXINE USING ORGANOCATALYST
-
The patent discloses an asymmetric synthesis of (-)-venlafaxine using an organocatalyst via a unified strategy employing organcatalytic Michael addition, regio-selective dehydration and selective epoxide ring opening.
- -
-
-
- Asymmetric total synthesis of (-)-venlafaxine using an organocatalyst
-
An asymmetric total synthesis of (-)-venlafaxine using an organocatalyst has been achieved via a unified strategy employing organcatalytic Michael addition, regio-selective dehydration and selective epoxide ring opening.
- Chavan, Subhash P.,Garai, Sumanta,Pawar, Kailash P.
-
p. 2137 - 2139
(2013/05/21)
-
- Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues
-
Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue have been reported in this communication. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.
- Bhuniya, Rajib,Nanda, Samik
-
scheme or table
p. 1990 - 1992
(2012/05/05)
-
- N-OXIDES OF VENLAFAXINE AND O-DESMETHYLVENLAFAXINE AS PRODRUGS
-
Embodiments of the invention relate to a compound of formula (1), or a tautomer, stereoisomer, hydrate, or solvate thereof, wherein R1 is H or CH3. Other embodiments of the invention relate to a pharmaceutical composition containing these compound, to methods for preparing these compounds, and to methods for preparing compositions containing these compounds. Yet other embodiments of the invention relate to the uses of these compounds and compositions containing it, such as for the manufacture of medicaments and pharmaceutical compositions for treating a condition chosen from depression, major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder, social anxiety disorder, panic disorder, general depressive disorders, diabetic neuropathy, migraine and hot flashes.
- -
-
Page/Page column 7
(2009/01/24)
-
- SOLID FORMS COMPRISING (-) O-DESMETHYLVENLAFAXINE AND USES THEREOF
-
Solid forms comprising a compound useful in the treatment, prevention and management of various conditions and diseases are provided herein. In particular, the invention provides solid forms comprising (-)-O-desmethylvenlafaxine, including salts thereof, having utility for the treatment, prevention and management of conditions and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
- -
-
Page/Page column 63
(2008/12/08)
-
- Process for selective synthesis of enantiomers of substituted 1-(2-amino-1-phenyl-ethyl)-cyclohexanols
-
A process for the enantioselective synthesis of an (S)— or (R)-1-[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol and analogues or salt thereof are described. The method involves the steps of (a) reacting an (S) or (R) 4-benzyloxazolidinone with a mixed anhydride of a methyoxyphenylacetic acid under conditions which form a oxazolidinone, (4S)— or (4R)-4-benzyl-3-[methyoxyphenyl]acetyl]-oxazolidin-2-one, (b) treating the (4S)— or (4R)-4-benzyl-3-[(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one with an aprotic amine base and titanium chloride in a chlorinated solvent under conditions which permit formation of the corresponding anion, (c) mixing the corresponding anion with titanium chloride and cylcohexanone under conditions which permit an aldol reaction to form the corresponding (4S)— or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one, (d) hydrolyzing the (4S)— or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one to form a chiral acid (2S or 2R)-(1-hydroxycyclohexyl)-methoxyphenyl)acetic acid, (e) coupling the chiral phenylacid to a secondary amine to form an amide, and (f) reducing the amide to form an (S) or (R) 1[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol or a salt thereof.
- -
-
Page/Page column 8; 9
(2008/06/13)
-
- Enantioselective synthesis of β-amino esters and its application to the synthesis of the enantiomers of the antidepressant Venlafaxine
-
β-Amino esters are readily formed from the rhodium(ii) prolinate-catalyzed intermolecular C-H insertion between methyl aryldiazoacetates and a bis-silyl protected methylamine. The Royal Society of Chemistry 2006.
- Davies, Huw M. L.,Ni, Aiwu
-
p. 3110 - 3112
(2008/09/20)
-
- Enantiomers of O-desmethyl venlafaxine
-
This invention provides pharmaceutically active enantiomers of the venlafaxine metabolite O-Desmethyl venlafaxine, R(?)-4-[2-(Dimethylamnino-1-(1-hydroxycyclo-hexyl)ethyl]phenol or R(?)1-[2-(dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclo-hexanol, and S(+)-1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol or S(+)-4-[2-(Dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol, or one or more pharmaceutically acceptable salts or salt hydrates thereof, as well as pharmaceutical compositions utilizing these enantiomers and methods of using the enantiomers to treat, inhibit or control central nervous system disorders.
- -
-
-
- 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: Synthesis and antidepressant activity
-
A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models - the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
- Yardley,Morris Husbands,Stack,Butch,Bicksler,Moyer,Muth,Andree,Fletcher III,James,Sielecki
-
p. 2899 - 2905
(2007/10/02)
-