- Continuous Flow Synthesis of ACE Inhibitors From N-Substituted l-Alanine Derivatives
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A strategy for the continuous flow synthesis of angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs in the range of ≈0.5 g h?1, all while avoiding both isolation of reactive intermediates and process intensive reaction conditions. The process was further developed by preparing enalapril, a World Health Organization (WHO) essential medicine, in an industrially relevant flow platform that scaled throughput to ≈1 g h?1.
- Breen, Christopher P.,Jamison, Timothy F.
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supporting information
p. 14527 - 14531
(2019/11/03)
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- Asymmetric synthesis of (S,S,S)-2-Aza-bicyclo-[3.3.0]-octane-3-carboxylic acid benzyl ester: Formal synthesis of ramipril
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An asymmetric synthesis of (S,S,S)-2-aza-bicyclo-[3.3.0]-octane-3- carboxylic acid benzyl ester 2 as an intermediate of angiotensin converting enzyme (ACE) inhibitor, ramipril 1, is described.
- Kondaiah,Vivekanandareddy,Reddy, L. Amarnath,Anurkar, Smita V.,Gurav,Ravikumar,Bhattacharya, Apurba,Bandichhor, Rakeshwar
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p. 1186 - 1191
(2011/05/05)
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- METHOD FOR THE SYNTHESIS OF A RAMIPRIL INTERMEDIATE
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The present invention relates to a process for the preparation of octahydrocyclopenta[b]pyrrole-2-carboxylic acid and esters thereof of general formula (1) in the presence of a cobalt and/or nickel comprising catalyst and to the use of compounds of general formula (1) in the synthesis of ramipril.
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Page/Page column 10-12
(2010/05/14)
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- NOVEL CARBAMOYLGLYCINE DERIVATIVES
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The present invention relates to carbamoylglycine derivatives, a process for the preparation of carbamoylglycine derivatives and the use of carbamoylglycine derivatives in the preparation of enantiomerically enriched α-amino acids. Furthermore, the present invention relates to the preparation of pharmaceutically active products such as perindopril and ramipril using the novel carbamoylglycine derivatives.
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Page/Page column 13
(2009/05/28)
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- IMPROVED RAMIPRIL SYNTHESIS
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The present invention relates to the preparation of ramipril (formula [1]) from unprotected (2S,3S,6S)-octahydrocyclopenta[b]pyrrole-2-carboxylic acid and to a method for preparing unprotected (2S,3S,6S)-octahydrocyclopenta[b]pyrrole-2- carboxylic acid.
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Page/Page column 6
(2009/06/27)
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- NOVEL CYCLOALKANONE β-SUBSTITUTED ALANINE DERIVATIVES
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The present invention relates to cycloalkanone β-substituted alanine derivatives, a process for the preparation of cycloalkanone β-substituted alanine derivatives and the use of cycloalkanone β-substituted alanine derivatives in the preparation of enantiomerically enriched α-amino acids. Furthermore, the present invention relates to the preparation of pharmaceutically active products such as perindopril and ramipril using the novel cycloalkanone β-substituted alanine derivatives.
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Page/Page column 8
(2009/10/09)
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- METHOD FOR THE PRODUCTION OF RAMIPRIL
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An improved method for preparing ramipril is disclosed, and also an intermediate for use in the method.
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Page/Page column 6
(2009/01/24)
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- NOVEL 5-SUBSTITUTED HYDANTOINS
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The present invention relates to 5-substituted hydantoins, a process for the preparation of 5-substituted hydantoins and the use of 5-substituted hydantoins in the preparation of enantiomerically enriched α-amino acids. Furthermore, the present invention relates to the preparation of pharmaceutically active products such as perindopril and ramipril using the novel 5-substituted hydantoins.
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Page/Page column 17-18
(2009/01/24)
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- Process for the preparation of bicyclic amino carboxylic acids, intermediates in this process, and their use
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The invention relates to a process for the preparation of compounds of the formula I STR1 in which n denotes 1, 2 or 3, R denotes acyl, and R1 denotes alkyl, cycloalkyl, aralkyl or another carboxyl protective group, which comprises radical cycl
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- Enantioselective synthesis of 1S, 3S, 5S- and 1R, 3S, 5R-2-Azabicyclo[3.3.0]octane-3-carboxylic acid starting from L-serine
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(1S, 3S, 5S)- and (1R, 3S, 5R)-2-Azabicyclo[3.3.0]octane-3-carboxylic acid have been synthesized by intramolecular radical cyclisation of methyl 2-(S)-[N-benzyloxycarbonyl-N-(2-cyclopenten-l-yl)amino]-3-iodopropionate and subsequent reactions.
- Urbach, Hansjoerg,Henning, Rainer
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p. 957 - 965
(2007/10/02)
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- COUPLING OF β-ACETAMIDO RADICALS WITH α-CHLORO ACRYLONITRILE - A NEW ACCESS TO DISUBSTITUTED PROLINE DERIVATIVES
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β-Acetamido radicals are prepared by reduction of organomercurials and coupled with α-chloro-acrylonitrile.The coupling products are further converted to proline derivatives.
- Henning, R.,Urbach, H.
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p. 5343 - 5346
(2007/10/02)
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