Asymmetric synthesis of esomeprazole

Cotton, Hanna K.; Elebring, Thomas; Larsson, Magnus; Li, Lanna; Sörensen, Henrik; Unge, Sverker von

doi:10.1016/s0957-4166(00)00352-9

Cited by 249 publications

(162 citation statements)

References 11 publications

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“…The diisopropyl tartratecatalyzed reaction was chosen for further optimization. Consistent with previous reports, addition of diisopropylethylamine to the reaction mixture dramatically improved the ee (22)(23)(24). The reaction could be conducted in a variety of solvents, including THF, ethyl acetate, and chlorobenzene, with only small differences in the ee.…”

Section: Preparation Of Benzoxathiin 6 Preparation Of This Key Intersupporting

confidence: 71%

“…The most practical process to make chiral sulfoxides from sulfides is the Kagan oxidation catalyzed by titanium(IV) isopropoxide and chiral diol ligands. A survey of the literature indicated that reaction conditions have to be carefully optimized for each substrate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Our preliminary screening of ligands under the original Kagan conditions (20,21) revealed that diisopropyl tartrate gave an ee of 38% and diethyl tartrate gave slightly lower ee.…”

Section: Preparation Of Benzoxathiin 6 Preparation Of This Key Intermentioning

confidence: 99%

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An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction

Song

King²,

Waters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an ␣,␤-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols. E strogen receptors (ERs) are members of the steroid hormone nuclear receptor superfamily. They are ligand-dependent transcription factors that bind to specific DNA sequences and regulate gene expression. There are two known members of the estrogen receptor family, ER␣ and ER␤, encoded by distinct genes. ER modulators are potentially useful agents for treatment or prevention of a variety of conditions related to estrogen functions, including bone loss, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of low-density lipoprotein cholesterol, cardiovascular disease, obesity, incontinence, and cancer (refs. 1-4 and references cited in ref. 4). SERMs are ER ligands that act like estrogens in some tissues, but block estrogen action in others. Thus, SERMs may exhibit an agonistic or antagonistic activity, depending on the context in which their activity is examined. Fig. 1) is a potent ER␣ SERM being evaluated as part of the selective ER antagonist program at Merck (1-4). Although there are several methods for the synthesis of the core cis-2,3-disubstituted-dihydrobenzoxathiin, the asymmetric synthesis of these compounds has not been reported (1-7). Herein, we report an enantioselective synthesis of 1. Experimental ProceduresGeneral. Chemicals were used as received from commercial sources unless otherwise noted. NMR data were collected on Bruker Avance NMR spectrometers. Chemical shifts are reported in ppm downfield from tetramethylsilane. HPLC purity data are reported as area percentage of the desired peak from the total peaks. HPLC conditions are listed in supporting information, which is published on the PNAS web site. High-resolution mass spectrometer (HRMS) data were collected on a Micromass API US Ultima quadrupole time-of-flight (QTOF) mass spectrometer. Vinyl Sulfide 6.A 100-liter round-bottom flask was charged with ketone 7 (8.01 kg, 12.2 mol) and 48 liters of acetonitrile followed by phenylphosphonic dichloride (2.50 kg, 12.9 mol). The flask was fitted with a reflux condenser with off-gases vented through a caustic scrubber, and the reaction mixture was heated to reflux (75°C). After about 2 h, HPLC assay showed Ͼ99% conversion. The reaction mixture was concentrated under reduced pressure at 20-50°C to 28 liters. Diisopropylethylamine (786 g, 6.08 mol) was added, followed by 28 liters of denatured ethanol (denatured with 0.5% toluene). The solution was ...

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Section: Preparation Of Benzoxathiin 6 Preparation Of This Key Intersupporting

confidence: 71%

Section: Preparation Of Benzoxathiin 6 Preparation Of This Key Intermentioning

confidence: 99%

An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction

Song

King²,

Waters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…The power of this methodology will only be fully realised when enantiopure sulfoxides are used. In that context, it is noteworthy that highly enantioselective methods for the oxidation of imidazolyl 11,12 and benzimidazolyl 12 sulfides have been developed. Future efforts will be focused on the use of enantiopure sulfoxides, and the development of Type II MIRC reactions.…”

Section: Discussionmentioning

confidence: 99%

MIRC reactions using sulfoxides and synthesis of dictyopterene A

Casey¹,

Keaveney²,

Walker³

2002

Arkivoc

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Michael initiated ring closure reactions, using alkyl imidazolyl sulfoxides as nucleophiles, provided a 2-substituted cyclopropanecarboxylate 2 and cyclohexanecarboxylate 5, with high yields and excellent diastereoselectivity. Thermal elimination of the imidazolylsulfinyl group gave an alkene 3. This method was used to carry out a short synthesis of dictyopterene A. A 2-hexenylcyclopropanecarboxylate 13 was prepared using a MIRC reaction of hexyl 1-methyl-2-imidazolyl sulfoxide with 4-bromocrotonate, followed by pyrolytic elimination of the imidazolylsulfinyl group. Straightforward conversion of the ester group into a vinyl group furnished dictyopterene A.

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“…45 The method used is based on the Kagan method, however the catalyst complex is prepared in the presence of the sulfide at an elevated temperature. The oxidation is carried out in the presence of N,N-diisopropylamine at 30 o C (Scheme 14).…”

Section: Scheme 13mentioning

confidence: 99%

Synthesis of enantioenriched sulfoxides

O’Mahony¹,

Kelly²,

Lawrence³

et al. 2011

Arkivoc

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This review discusses strategies for the asymmetric synthesis of sulfoxides, compounds with many applications in stereoselective synthesis and in some cases with pharmaceutical application. The review describes asymmetric oxidation, including metal catalyzed and nonmetal and biological oxidation processes, in addition to synthetic approaches via nucleophilic substitution of appropriately substituted precursors. Kinetic resolution in oxidation of sulfoxides to the analogous sulfones is also discussed; in certain instances, access to enantioenriched sulfoxides can be achieved via a combination of asymmetric sulfide oxidation and complementary kinetic resolution in sulfoxide oxidation.

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Asymmetric synthesis of esomeprazole

Cited by 249 publications

References 11 publications

An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction

An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction

MIRC reactions using sulfoxides and synthesis of dictyopterene A

Synthesis of enantioenriched sulfoxides

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