Asymmetric synthesis of (-)-(R)-sitagliptin
The asymmetric synthesis of (-)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N- (α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p- methoxybenzyl)amide to ter...
| Main Authors: | , , , , |
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| Formato: | Journal article |
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2012
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| _version_ | 1826278953151627264 |
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| author | Davies, S Fletcher, A Lv, L Roberts, P Thomson, J |
| author_facet | Davies, S Fletcher, A Lv, L Roberts, P Thomson, J |
| author_sort | Davies, S |
| collection | OXFORD |
| description | The asymmetric synthesis of (-)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N- (α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p- methoxybenzyl)amide to tert-butyl 4-(2′,4′,5′-trifluorophenyl) but-2-enoate to install the correct stereochemistry. Subsequent sequential acid-catalysed hydrolysis of the resultant β-amino esters, HOBt/EDC mediated coupling with the triazolopyrazine fragment, and hydrogenolysis gave (-)-(R)-sitagliptin in 43% and 42% overall yields, respectively. © 2012 Elsevier Ltd. All rights reserved. |
| first_indexed | 2024-03-06T23:51:36Z |
| format | Journal article |
| id | oxford-uuid:72c9f46e-bb4b-4e9f-b1db-87304f3fae23 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:51:36Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:72c9f46e-bb4b-4e9f-b1db-87304f3fae232022-03-26T19:52:21ZAsymmetric synthesis of (-)-(R)-sitagliptinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:72c9f46e-bb4b-4e9f-b1db-87304f3fae23Symplectic Elements at Oxford2012Davies, SFletcher, ALv, LRoberts, PThomson, JThe asymmetric synthesis of (-)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N- (α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p- methoxybenzyl)amide to tert-butyl 4-(2′,4′,5′-trifluorophenyl) but-2-enoate to install the correct stereochemistry. Subsequent sequential acid-catalysed hydrolysis of the resultant β-amino esters, HOBt/EDC mediated coupling with the triazolopyrazine fragment, and hydrogenolysis gave (-)-(R)-sitagliptin in 43% and 42% overall yields, respectively. © 2012 Elsevier Ltd. All rights reserved. |
| spellingShingle | Davies, S Fletcher, A Lv, L Roberts, P Thomson, J Asymmetric synthesis of (-)-(R)-sitagliptin |
| title | Asymmetric synthesis of (-)-(R)-sitagliptin |
| title_full | Asymmetric synthesis of (-)-(R)-sitagliptin |
| title_fullStr | Asymmetric synthesis of (-)-(R)-sitagliptin |
| title_full_unstemmed | Asymmetric synthesis of (-)-(R)-sitagliptin |
| title_short | Asymmetric synthesis of (-)-(R)-sitagliptin |
| title_sort | asymmetric synthesis of r sitagliptin |
| work_keys_str_mv | AT daviess asymmetricsynthesisofrsitagliptin AT fletchera asymmetricsynthesisofrsitagliptin AT lvl asymmetricsynthesisofrsitagliptin AT robertsp asymmetricsynthesisofrsitagliptin AT thomsonj asymmetricsynthesisofrsitagliptin |