cas 172900-71-9, Benzenepropanoic acid, 4-methoxy-3-(3-methoxypropoxy)-a-(1-methylethyl)-, (aR)-

Articles about 172900-71-9Total 28 be found

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Synthesis of enantiopure (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid-a key intermediate for the preparation of Aliskiren
The enantioselective hydrogenation of (E)-2-(4-methoxy-3-(3-methoxypropoxy)-benzylidene)-3-methylbutanoic acid (1) to (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid (2)-a key intermediate in the synthesis of the pharmacologically important renin inhibitor Aliskiren-is described. The stereochemistry of the catalytic transformation has been studied using a number of homogeneous chiral Rh(I) and Ru(II) complexes bearing ferrocene-based phosphine ligands. The highest enantioselectivity for the homogeneous hydrogenation of 1 (up to 95% ee) was achieved with a [Rh(NBD)2]BF4 pre-catalyst (substrate/catalyst ratio 100:1, 10 bar H2, 40 °C, in MeOH). To bring the enantioselectivity to perfection an effective method for the isolation of the enantiopure carboxylic acid is suggested likewise.
Andrushko, Natalia,Andrushko, Vasyl,Thyrann, Thomas,K?nig, Gerd,B?rner, Armin
p. 5980 - 5982
(2008)
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A mixed-ligand approach enables the asymmetric hydrogenation of an α-isopropylcinnamic acid en route to the renin inhibitor aliskiren
An asymmetric hydrogenation process for the α-isopropyl dihydrocinnamic acid derivative 2, an intermediate for the renin inhibitor aliskiren (4), has been developed using a rhodium catalyst ligated with a chiral monodentate phosphoramidite and a nonchiral phosphine. Whereas catalysts based on two equivalents of monodentate phosphoramidites gave promising results, the rate of hydrogenation and ee of the product could be improved spectacularly by the addition of monodentate non-chiral triarylphosphines to these catalysts. This remarkable mixed-ligand catalyst has been identified using high-throughput experimentation. With the best catalysts turnover numbers >5000 mol mol -1, turnover frequencies >1000 mol mol-1 h -1, and ee's up to 95% have been achieved.
Boogers, Jeroen A. F.,Felfer, Ulfried,Kotthaus, Martina,Lefort, Laurent,Steinbauer, Gerhard,De Vries, Andre H. M.,De Vries, Johannes G.
p. 585 - 591
(2007)
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A aliskiren or its salt separation and analysis method
The invention relates to a separation analysis method using polysaccharide derivative-bonded and coated silica as a stationary phase and an organic solvent as a mobile phase for separation analysis of aliskiren and isomers thereof, effective separation of the aliskiren and isomers thereof can be realized, and the separation analysis method has the important meaning to the product quality control.
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(2017/08/25)

Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5-C6 Disconnection and CO2H-NH2 Equivalence
A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which the C5 carbon acts as a nucleophile and the amino group is introduced by a Curtius rearrangement, which follows a simultaneous stereocontrolled generation of the C4 and C5 stereogenic centers by an asymmetric hydrogenation. Operational simplicity, step economy, and a good overall yield makes this synthesis amenable to manufacture on scale.
Cini, Elena,Banfi, Luca,Barreca, Giuseppe,Carcone, Luca,Malpezzi, Luciana,Manetti, Fabrizio,Marras, Giovanni,Rasparini, Marcello,Riva, Renata,Roseblade, Stephen,Russo, Adele,Taddei, Maurizio,Vitale, Romina,Zanotti-Gerosa, Antonio
supporting information
p. 270 - 283
(2016/03/04)

Walphos versus biferrocene-based walphos analogues in the asymmetric hydrogenation of alkenes and ketones
Two representative Walphos analogues with an achiral 2,2″- biferrocenediyl backbone were synthesized. These diphosphine ligands were tested in the rhodium-catalyzed asymmetric hydrogenation of several alkenes and in the ruthenium-catalyzed hydrogenation of two ketones. The results were compared with those previously obtained on using biferrocene ligands with a C 2-symmetric 2,2″-biferrocenediyl backbone as well as with those obtained with Walphos ligands. The application of one newly synthesized ligand in the hydrogenation of 2-methylcinnamic acid gave (R)-2-methyl-3- phenylpropanoic acid with full conversion and with 92% ee. The same ligand was used to transform 2,4-pentanedione quantitatively and diastereoselectively into (S,S)-2,4-pentanediol with 98% ee.
Zirakzadeh, Afrooz,Gross, Manuela A.,Wang, Yaping,Mereiter, Kurt,Weissensteiner, Walter
p. 1945 - 1952
(2014/05/20)

NOVEL PROCESS FOR THE PREPARATION OF RENIN INHIBITORS
The present invention relates to an improved process for the preparation of compound of Formula-II, which is an intermediate in the preparation of Aliskiren and further conversion of compound of Formula-II into Aliskiren or its pharmaceutically acceptable salts. Formula-II wherein Ri and R2 are independently of one another H, Ci-C6 alkyl, C- C6 halogenalkyl, C]-C6 alkoxy, Ci-C6 alkoxy-Ci-C6 alkyl, or Ci-C6 alkoxy-Ci- C6 alkyloxy and X is halogen selected from fluoro, chloro, bromo and iodo
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(2013/08/28)

AN IMPROVED PROCESS FOR THE PREPARATION OF ALISKIREN
The present invention relates to an improved process for the preparation of renin inhibitor Aliskiren intermediates of Formula-II and further conversion into Aliskiren and its pharmaceutically acceptable salts.
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(2013/12/03)

An improved and economical process for the manufacture of the key intermediate of aliskiren, a new potent renin inhibitor
An improved, practical, economical and efficient process for the production of (2S,4S)-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoic acid, a key intermediate of the new potent renin inhibitor of aliskiren, in a total yield over 30% is described. This process avoids expensive reagents and chromatographic purifications, and is easily scaled up in industry.
Wang, Fan,Xu, Xiao-Ying,Wang, Fei-Ying,Peng, Lin,Zhang, Yong,Tian, Fang,Wang, Li-Xin
p. 1458 - 1462
(2013/12/04)

Biferrocene-based diphosphine ligands: Synthesis and application of walphos analogues in asymmetric hydrogenations
A total of four biferrocene-based Walphos-type ligands have been synthesized, structurally characterized, and tested in the rhodium-, ruthenium- and iridium-catalyzed hydrogenation of alkenes and ketones. Negishi coupling conditions allowed the biferrocene backbone of these diphosphine ligands to be built up diastereoselectively from the two nonidentical and nonracemic ferrocene fragments (R)-1-(N,N-dimethylamino)ethylferrocene and (SFc)-2- bromoiodoferrocene. The molecular structures of (SFc)-2- bromoiodoferrocene, the coupling product, two ligands, and the two complexes ([PdCl2(L)] and [RuCl(p-cymene)(L)]PF6) were determined by X-ray diffraction. The structural features of complexes and the catalysis results obtained with the newly synthesized biferrocene-based ligands were compared with those of the corresponding Walphos ligands.
Zirakzadeh, Afrooz,Gross, Manuela A.,Wang, Yaping,Mereiter, Kurt,Spindler, Felix,Weissensteiner, Walter
supporting information
p. 1075 - 1084
(2013/04/23)

ChenPhos: Highly modular P-stereogenic C1-symmetric diphosphine ligands for the efficient asymmetric hydrogenation of α-substituted cinnamic acids
These cats are purrfectionists: The ChenPhos ligands (see structure) showed dramatically higher catalytic activity in the title reaction than their C 2-symmetric predecessor with two dimethylaminoethyl-substituted ferrocenyl(phenyl)phosphanyl groups. The ready accessibility, extreme air stability, and high enantioselectivity, activity, and productivity of these ligands make them very promising for a wide range of practical applications. Copyright
Chen, Weiping,Spindler, Felix,Pugin, Benoit,Nettekoven, Ulrike
supporting information
p. 8652 - 8656
(2013/09/12)

Process for Producing Aliskiren
A new route of synthesis of the compound Aliskiren of formula (I), used in the treatment of hypertension, is described.
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Paragraph 0095-0107

(2013/03/28)

A PROCESS FOR THE PREPARATION OF INTERMEDIATES USEFUL IN THE PRODUCTION OF ALISKIREN
A process for preparing 4-[(2R)-2-X-methyl)-3-methylbutyl]-1 -methoxy-2-3(3- methoxypropoxy)-benzene wherein X is a leaving group and use of this compound in the synthesis of aliskiren.
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(2012/06/30)

PROCESS FOR PRODUCING ALISKIREN
A new route of synthesis of the compound Aliskiren of formula (I), used in the treatment of hypertension, is described.
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Page/Page column 20-21

(2011/12/14)

PROCESS FOR THE PREPARATION OF (2S,4S,5S,7S)-N-(2-CARBAMYL-2- METHYLPROPYL)-5-AMINO-4-HYDROXY-2,7-DIISOPROPYL-8-[4-METHOXY-3-(3- METHOXYPROPOXY)PHENYL]-OCTANAMIDE HEMIFUMARATE AND ITS INTERMEDIATES THEREOF
The present invention relates to a process for the preparation of (2S,4S,5S,7S)-N-(2- Carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxy propoxy )phenyl]-octanamide compound of formula- 1 and its pharmaceutically acceptable salts thereof. Further, relates to the processes for the preparation of (R)-4-(2-(halomethyl)-3- methylbutyl)-l-methoxy-2-(3-methoxypropoxy) benzene and (R)-2-(4-methoxy-3-(3-methoxy propoxy) benzyl)-3-methyIbutan-l-ol useful intermediates in the synthesis of compound of formula- 1.
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(2011/12/14)

APPLICATION OF THE IRIDIUM COMPLEX IN ASYMMETRIC CATALYTIC HYDROGENATION FOR UNSATURATED CARBOXYLIC ACID
The present invention relates to a preparation method of carboxylic acids with optical activity, particularly, publishes that very useful chiral carboxylic acids can be obtained by the asymmetric catalytic hydrogenation of tri-substituted α,β-unsaturated carboxylic acids, with the complexes of the chiral phosphor nitrogen ligands and iridium used as the catalysts which show high activity and enantioselectivity (up to 99.8% ee), thus provides a more efficient method with higher enantioselectivity for asymmetric catalytic hydrogenation of chiral carboxylic acid-like compounds, and has important application value to asymmetric hydrogenation of chiral carboxylic acids.
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Page/Page column 19-20

(2011/02/18)

Acid promoted CIDT for the deracemization of dihydrocinnamic aldehydes with Betti's base
Racemic α-epimerizable and unfunctionalized aldehydes have been converted into enantiomerically enriched mixtures through a sequence of (i) a conversion into the diastereoisomeric 3-substituted 1-phenyl-2,3-dihydro-1H- naphtho[1,2-e][1,3]oxazines by reaction with the (R)- or (S)-1-(α- aminobenzyl)-2-naphthol (Betti's base), (ii) an acid promoted crystallization-induced diastereoisomer transformation (CIDT), and (iii) a clean cleavage of the dihydro-1,3-naphthoxazinic ring of the enriched diastereoisomer, easily collected by filtration, allowing the recovery of the enantiomerically enriched aldehydes and the chiral auxiliary.
Rosini, Goffredo,Paolucci, Claudio,Boschi, Francesca,Marotta, Emanuela,Righi, Paolo,Tozzi, Francesco
scheme or table
p. 1747 - 1757
(2011/02/28)

Iridium-catalyzed enantioselective hydrogenation of α,β- unsaturated carboxylic acids
A highly efficient iridium-catalyzed hydrogenation of α,β-unsaturated carboxylic acids has been developed by using chiral spiro-phosphino-oxazoline ligands, affording α-substituted chiral carboxylic acids in exceptionally high enantioselectivities and reactivities. Copyright
Li, Shen,Zhu, Shou-Fei,Zhang, Can-Ming,Song, Song,Zhou, Qi-Lin
supporting information; experimental part
p. 8584 - 8585
(2009/02/03)

PROCESS FOR PREPARING (R OR S)-2-ALKYL-3-HETEROCYCLYL-1-PROPANOLS
Compounds of the formula (I) in which R'1, R'2,R'3 and Het are each defined as specified in the description are obtainable in high yields by a stereoselective addition of R'3-substituted propionic esters onto R'1- and R'2-substituted unsaturated, bicyclic heterocyclylaldehydes of the formula R-CHO to give corresponding 3-(R)-3-hydroxy-2-R'3-propionic esters. Conversion of the OH group to a leaving group, a subsequent regioselective elimination to give 3-(R)-2-R'3-propenoic esters, followed by: 1) hydrolysis to the corresponding 3-(R)-2-R'3-propenoic acids, their enantioselective hydrogenation to corresponding chiral 3-(R)-2-R'3-propenoic acids and their reduction, or 2) hydrolysis to the corresponding 3-(R)-2-R'3-propenoic acids, their reduction to corresponding 3-(R)-2-R'3-allylalcohols and their enantioselective hydrogenation, or 3) reduction to corresponding 3-(R)-2-R'3-allylalcohols and their enantioselective hydrogenation, where R is formula (II) and the enantioselective hydrogenations are performed with metal complexes which have, as ligands, ferrocene-1,1'-diphosphines which have, in the 1-position, a ferrocene-substituted secondary phosphine group and, in the1'-position, a secondary phosphine group.
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Page/Page column 57-59; 60

(2008/12/06)

FERROCENEDIPHOSPHINES
Compounds of the formula I in the form of enantiomerically pure diastereomers or a mixture of diastereomers, (I), where the radicals R1 are identical or different and are each C1-C4-alkyl; m is 0 or an integer from 1 to 3; n is 0 or an integer from 1 to 4; R2 is a hydrocarbon radical or a C-bonded heterohydrocarbon radical; Cp is unsubstituted or C1-C4-alkyl-substituted cyclopentadienyl; Y is a C-bonded chiral group which directs metals of metallation reagents into the ortho position; and Phos is a P-bonded P(III) substituent. The compounds are chiral ligands for complexes of transition metals which are used as homogeneous catalysts in asymmetric syntheses.
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Page/Page column 41-42

(2008/06/13)

Stereoselective synthesis of ferrocene-based C2-symmetric diphosphine ligands: Application to the highly enantioselective hydrogenation of α-substituted cinnamic acids
(Chemical Equation Presented) Chirality3: A new ferrocene-based diphosphine ligand is applied to the asymmetric hydrogenation of α-substituted cinnamic acids. The P-centered-, C-centered-, and planar-chiral ligand (RC,RC,SFc,S Fc,SP,SP)-1 displays unprecedented enantioselectivity in this Rh-catalyzed reaction (see scheme; cod = cycloocta-1,5-diene).
Chen, Weiping,McCormack, Peter J.,Mohammed, Karim,Mbafor, William,Roberts, Stanley M.,Whittall, John
p. 4141 - 4144
(2008/03/11)

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-PHENYLPROPIONIC ACID DERIVATIVES AND FOLLOW-ON PRODUCTS OF THE LATTER
The invention relates to a method for producing optically active 3-phenylpropionic acid derivatives, to optically active 1-chloro-3-phenylpropane derivatives that are obtained from the latter and to optically active intermediate products that are obtained by said method.
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Page/Page column 28; 31-32

(2008/06/13)

PROCESS FOR THE MANUFACTURE OF SUBSTITUTED PROPIONIC ACIDS
The invention concerns a process for the manufacture of substituted propionic acids comprising providing a substrate of formula (I): And subjecting the substrate to enantioselective hydrogenation under enantioselective hydrogenation conditions in the presence of an enantioselective hydrogenation catalyst comprising a catalyst ligand having a metallocene group with a chiral phosphorus or arsenic substituent to provide in enantiomeric excess a product of formula (II): or its enantiomer or if applicable its diastereomer.
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Page/Page column 32; 33-34

(2008/06/13)

METALLOCENE-BASED PHOSPHORUS CHIRAL PHOSPHINES
The present invention concerns a metallocene-based phosphine ligand for use in enantioselective catalysis, the ligand having the Formula (I): Wherein M is a metal; Z is P or As; L is a suitable linker; R1 is selected from alkyl, alkoxy, alkylamino, cycloalkyl, cycloalkoxy, cycloalkylamino carbocyclic aryl, substituted and unsubstituted carbocyclic aryloxy, heteroaryl, heteroaryloxy, carbocyclic arylamino and heteroarylamino; X* is selected from (II): Wherein R, R2 and R3 are independently selected from optionally substituted branched- and straight-chain alkyl, cycloalkyl, heterocycloalkyl, carbocyclic aryl, and heteroaryl.
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Page/Page column 19-20; 23

(2008/06/13)

Practical synthesis of an orally active renin inhibitor aliskiren
A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization.
Dong, Hua,Zhang, Zhi-Liu,Huang, Jia-Hui,Ma, Rujian,Chen, Shu-Hui,Li, Ge
p. 6337 - 6340
(2007/10/03)

The nonchiral bislactim diethoxy ether as a highly stereo-inducing synthon for sterically hindered, γ-branched α-amino acids: A practical, large-scale route to an intermediate of the novel renin inhibitor aliskiren
The diastereoselective synthesis of the sterically hindered, γ-branched α-amino acid derivative (2S,4S)-24a and its N-[(tert-butoxy)carbonyl](Boc)-protected alcohol (2S,4S)-19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)-17 was obtained by alkylation of the chiral Schoellkopf dihydropyrazine (R)-12a with the dialkoxy-substituted alkyl bromide (R)-11a, which proceeded with explicitly high diastereofacial selectivity (ds > 98%) to give (2S,SR,2′S)-13a (Scheme 4), followed by mild acid hydrolysis and N-Boc protection (Scheme 5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)-11a with the enantiomeric (S)-12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeO-C(6) and the bulky residues of (R)-11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)-11a was found to provide a 95:5 mixture of diastereoisomers (2S,2′S)-22a and (2R,2′S)-23a in high yield (Scheme 6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)-24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)-28a and (R)-28b with both (R)-12a and (S)-12b as well as with the achiral 21 was investigated (Schemes 7-9). The precursor bromides (R)-11a, (S)-11b, (R)-28a, and (S)-28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)-7a and (S)-7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes 3 and 7). A practical and economical protocol of the preparation of (2S,4S)-24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N-protected γ-branched α-amino acid with (2S) absolute configuration.
Goeschke, Richard,Stutz, Stefan,Heinzelmann, Walter,Maibaum, Juergen
p. 2848 - 2870
(2007/10/03)

A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands for Rh- And Ru-Catalysed Enantioselective Hydrogenation
A series of diphosphines of the novel Walphos ligand family all based on a phenylferrocenylethyl backbone were synthesised in a four-step sequence. In the rhodium- or ruthenium-catalysed asymmetric hydrogenation of olefins and ketones enantioselectivities of up to 95% and 97%, respectively, were obtained. A 2-isopropylcinnamic acid derivative of industrial interest was hydrogenated in 95% ee and with turnover numbers of > 5000.
Sturm, Thomas,Weissensteiner, Walter,Spindler, Felix
p. 160 - 164
(2007/10/03)

METHODS OF TREATING ALZHEIMER'S DISEASE USING ARYL ALKANOIC ACID AMIDES
Disclosed are methods for treating Alzheimer’s disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of compounds of formula 1 (1) wherein the variables R1-R8 and X are defined herein.
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Page 234-235

(2010/02/05)