专利号:US-8017776-B2 优先权日:2003-07-15 标题 :Methods for synthesis of acyloxyalkyl compounds 发明人:BHAT LAXMINARAYAN; GALLOP MARK A 权利人:XENOPORT INC 摘要:Disclosed herein are methods for synthesizing 1-(acyloxy)-alkyl prodrug derivatives of drugs through oxidation of 1-acyl-alkyl derivatives of drugs under anhydrous reaction conditions. The methods typically proceed stereospecifically, in high yield, do not require the use of activated intermediates and/or toxic compounds and are readily amenable to scale-up.
专利号:US-4255594-A 优先权日:1979-09-18 标题 :Hydrogenation of halogen-containing carboxylic anhydrides 发明人:NOVOTNY MIROSLAV 权利人:ALLIED CHEM 摘要:A process is described for the heterogeneous hydrogenation of haloalkyl, halocycloalkyl or haloaryl carboxylic anhydrides to the corresponding primary alcohols. In the haloalkyl or halocycloalkyl carboxylic anhydrides at least one halogen is in the alpha-position relative to the carboxylic anhydride grouping. The hydrogenation can be carried out in the liquid or vapor phase in the presence of a supported or unsupported catalyst comprising a member of the group consisting of rhodium, iridium, metal oxides thereof, or mixtures thereof. In the liquid phase, the hydrogenation can be carried out batchwise under mild conditions of temperature and pressure, preferably at about 50°-150° C. and about 5-15 atmospheres, in an atmosphere containing hydrogen gas. A preferred embodiment is the hydrogenation of trifluoroacetic anhydride in the liquid phase to 2,2,2-trifluoroethanol, said alcohol being useful as an intermediate in the synthesis of the anesthetic, isoflurane, CF 3 CHClOCHF 2 .
专利号:EP-2354120-A1 优先权日:2003-08-20 标题 :Synthesis of acyloxyalkyl carbamate prodrugs and intermediates thereof 发明人:GALLOP MARK A; YAO FENMEI; LUDWIKOW MARIA J; PHAN THU; PENG GE 权利人:XENOPORT INC 摘要:The present invention relates to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-fluorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (±)-4-amino-3-(4-fluorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (±)-4-amino-3-(4-tluorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The present invention also relates to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-fluorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.
专利号:US-8372881-B2 优先权日:2005-06-20 标题 :Acyloxyalkyl carbamate prodrugs of tranexamic acid, methods of synthesis and use 发明人:ZERANGUE NOA; JANDELEIT BERND; LI YUNXIAO; GALLOP MARK A 权利人:XENOPORT INC; ZERANGUE NOA; JANDELEIT BERND; LI YUNXIAO; GALLOP MARK A 摘要:Acyloxyalkyl carbamate prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid, pharmaceutical compositions thereof, methods of making prodrugs of trans-4-(aminomethyl)-cyclohexane-carboxylic acid, and methods of using prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid and pharmaceutical compositions thereof to treat or prevent various diseases or disorders are disclosed. Acyloxyalkyl carbamate prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid and pharmaceutical compositions thereof suitable for oral and topical administration and for administration using sustained release dosage forms are also disclosed.
专利号:US-9944592-B2 优先权日:2003-08-20 标 题:Acyloxyalkyl carbamate prodrugs, methods of synthesis and use 发明人:GALLOP MARK A; YAO FENMEI; LUDWIKOW MARIA J; PHAN THU; PENG GE 权利人:XENOPORT INC 摘要:The disclosures herein relate generally to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The disclosures herein also relate to acyloxyalkyl carbamate prodrugs of (±)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.
专利号:US-7662987-B2 优先权日:2003-07-15 标题:Methods for synthesis of acyloxyalkyl compounds
参考标题:Facile Synthesis Of 1,1-Difluoroallenes Via The Difluorovinylidenation Of Aldehydes And Ketones 作者:Misaki Yokota,Kohei Fuchibe,Mikiko Ueda,Yuka Mayumi,Junji Ichikawa |发布日期:2009.9.3 摘要:2-Bromo-3,3-Difluoroallylic Acetates Were Readily Prepared By The Reaction Of Carbonyl Compounds With 1-Bromo-2,2-Difluorovinyllithium, Generated From 1,1-Dibromo-2,2-Difluoroethylene, Followed By Acetylation. On Treatment With Butyllithium, The Bromoacetates Underwent Selective 1,2-Elimination Of Lithium Acetate To Afford Mono- And Disubstituted 1,1-Difluoroallenes In High Yields.
合成参考文献
参考文献:10.1016/s1044-0305(99)00135-x 摘要:Weintraub ST, Satsangi RK, Sprague EA, Prihoda TJ, Pinckard RN. Mass spectrometric analysis of platelet-activating factor after isolation by solid-phase extraction and direct derivatization with pentafluorobenzoic anhydride. Journal of The American Society for Mass Spectrometry. 2000 Feb 01;11(2):176–81. doi: 10.1016/s1044-0305(99)00135-x.