合成路线:1.The nitration of isosorbide (I) with fuming HNO3 in acetic acid/acetic anhydride gives the dinitrate (II),which is selectively monoreduced by means of diisopropyltitanium tetrahydroborate (obtained by reaction of disopropyltitanium dichloride with benzyltriethylammonium borohydride) in dichloromethane to afford the isosorbide 5-nitrate.2.The reduction of dinitrate (II) can also be performed with benzyl triethyl ammonium tetrathiomolibdate in DMF.3.The reduction of dinitrate (II) can also be performed with H2 over PtO2/C in methanol.4.The reduction of dinitrate (II) can also be performed with cobalt phthalocyanine and NaBH4 in methanol.5.The reduction of dinitrate (II) can also be performed with Zn and HOAc in ethanol/water.6.The reduction of dinitrate (II) can also be performed with H2 over Pd/C and NiCl2 in ethanol/water.7.The reaction of isosorbide (I) with 4-nitrobenzoyl chloride (III) and pyridine in dichloromethane gives the isosorbide 2-O-(4-nitrobenzoate (IV),which is nitrated with HNO3 in acetic acid/acetic anhydride to yield the isosorbide 5-O-nitrate-2-O-(4-nitrobenzoate) (V).Finally,this compound is selectively hydrolyzed with KOH in methanol/dichloromethane.
参考文献标题:Process for the preparation of isosorbide-5-nitrate
文献作者:Gallardo Carrera,A.(Fordonal SL)
参考来源:ES 8402305
合成路线:1.The nitration of isosorbide (I) with fuming HNO3 in acetic acid/acetic anhydride gives the dinitrate (II),which is selectively monoreduced by means of diisopropyltitanium tetrahydroborate (obtained by reaction of disopropyltitanium dichloride with benzyltriethylammonium borohydride) in dichloromethane to afford the isosorbide 5-nitrate.2.The reduction of dinitrate (II) can also be performed with benzyl triethyl ammonium tetrathiomolibdate in DMF.3.The reduction of dinitrate (II) can also be performed with H2 over PtO2/C in methanol.4.The reduction of dinitrate (II) can also be performed with cobalt phthalocyanine and NaBH4 in methanol.5.The reduction of dinitrate (II) can also be performed with Zn and HOAc in ethanol/water.6.The reduction of dinitrate (II) can also be performed with H2 over Pd/C and NiCl2 in ethanol/water.7.The reaction of isosorbide (I) with 4-nitrobenzoyl chloride (III) and pyridine in dichloromethane gives the isosorbide 2-O-(4-nitrobenzoate (IV),which is nitrated with HNO3 in acetic acid/acetic anhydride to yield the isosorbide 5-O-nitrate-2-O-(4-nitrobenzoate) (V).Finally,this compound is selectively hydrolyzed with KOH in methanol/dichloromethane.
参考文献标题:Synthesis of isosorbide mononitrate
文献作者:Roberts,S.M.; Marston,R.W.; Quigley,P.F.; Brown,C.M.; Cross,S.J.(Clariant Life Science Molecules SpA)
参考来源:EP 1248788; WO 0149692
合成路线:8.The enantioselective monoacetylation of isosorbide (I) by means of vinyl acetate (VI) catalyzed by Pig liver esterase in dichloromethane gives isosorbide 2-O-acetate (VII),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-acetate-5-O-nitrate (VIII).Finally,this compound is deacetylated by means of K2CO3 in methanol.9.The enantioselective monoacylation of isosorbide (I) by means of vinyl butyrate (IX) catalyzed by Chiraclec-BL in THF or Carlsberg subtilisin in tert-butanol gives isosorbide 2-O-butyrate (X),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-butyrate-5-O-nitrate (XI).Finally,this compound is deacylated by means of K2CO3 in methanol.10.The acylation of isosorbide (I) with acetic anhydride and pyridine gives the diacetate (XII),which is enantioselectively monodeacetylated by means of lipase from Pseudomonas fluorescens in THF to yield isosorbide 2-O-acetate (VII).This compound is then nitrated to (VIII) and finally deacetylated as already described.11.The acylation of isosorbide (I) with HOAc and Ac2O gives (after purification by crystallization) isosorbide 2-O-acetate (VII),which is nitrated to (VIII) and finally deacetylated as already described.12.The acylation of isosorbide (I) with isobutyric acid (XIII) by means of sulfuric acid in refluxing chlorobenzene/toluene gives isosorbide 2-O-isobutyrate (XIV),which is nitrated with HNO3/H2SO4 to yield isosorbide 2-O-isobutyrate-5-O-nitrate (XV).Finally,this compound is deacylated by means of NaOH in toluene/water.13.The nitration of isosorbide (I) by means of HNO3 in HOAc/Ac2O gives a 3.5/1 mixture of isosorbide-5-O-nitrate and isosorbide 2-O-nitrate that is separated by column chromatography over alumina.14.The nitration of isosorbide (I) with HNO3 in benzene/HOAc/Ac2O,followed by a purification step yields the target isosorbide-5-O-nitrate.
参考文献标题:Synthesis of isosorbide cpds.
文献作者:Roberts,S.M.; Marston,R.W.; Quigley,P.F.; Brown,C.M.(Clariant Life Science Molecules SpA)
参考来源:GB 2358859
合成路线:8.The enantioselective monoacetylation of isosorbide (I) by means of vinyl acetate (VI) catalyzed by Pig liver esterase in dichloromethane gives isosorbide 2-O-acetate (VII),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-acetate-5-O-nitrate (VIII).Finally,this compound is deacetylated by means of K2CO3 in methanol.9.The enantioselective monoacylation of isosorbide (I) by means of vinyl butyrate (IX) catalyzed by Chiraclec-BL in THF or Carlsberg subtilisin in tert-butanol gives isosorbide 2-O-butyrate (X),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-butyrate-5-O-nitrate (XI).Finally,this compound is deacylated by means of K2CO3 in methanol.10.The acylation of isosorbide (I) with acetic anhydride and pyridine gives the diacetate (XII),which is enantioselectively monodeacetylated by means of lipase from Pseudomonas fluorescens in THF to yield isosorbide 2-O-acetate (VII).This compound is then nitrated to (VIII) and finally deacetylated as already described.11.The acylation of isosorbide (I) with HOAc and Ac2O gives (after purification by crystallization) isosorbide 2-O-acetate (VII),which is nitrated to (VIII) and finally deacetylated as already described.12.The acylation of isosorbide (I) with isobutyric acid (XIII) by means of sulfuric acid in refluxing chlorobenzene/toluene gives isosorbide 2-O-isobutyrate (XIV),which is nitrated with HNO3/H2SO4 to yield isosorbide 2-O-isobutyrate-5-O-nitrate (XV).Finally,this compound is deacylated by means of NaOH in toluene/water.13.The nitration of isosorbide (I) by means of HNO3 in HOAc/Ac2O gives a 3.5/1 mixture of isosorbide-5-O-nitrate and isosorbide 2-O-nitrate that is separated by column chromatography over alumina.14.The nitration of isosorbide (I) with HNO3 in benzene/HOAc/Ac2O,followed by a purification step yields the target isosorbide-5-O-nitrate.
参考文献标题:Process for the preparation of isosorbide-5-nitrate
文献作者:Stoss,P.(Heinrich Mack)
参考来源:DE 3102947; EP 0057847; US 4371703
合成路线:8.The enantioselective monoacetylation of isosorbide (I) by means of vinyl acetate (VI) catalyzed by Pig liver esterase in dichloromethane gives isosorbide 2-O-acetate (VII),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-acetate-5-O-nitrate (VIII).Finally,this compound is deacetylated by means of K2CO3 in methanol.9.The enantioselective monoacylation of isosorbide (I) by means of vinyl butyrate (IX) catalyzed by Chiraclec-BL in THF or Carlsberg subtilisin in tert-butanol gives isosorbide 2-O-butyrate (X),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-butyrate-5-O-nitrate (XI).Finally,this compound is deacylated by means of K2CO3 in methanol.10.The acylation of isosorbide (I) with acetic anhydride and pyridine gives the diacetate (XII),which is enantioselectively monodeacetylated by means of lipase from Pseudomonas fluorescens in THF to yield isosorbide 2-O-acetate (VII).This compound is then nitrated to (VIII) and finally deacetylated as already described.11.The acylation of isosorbide (I) with HOAc and Ac2O gives (after purification by crystallization) isosorbide 2-O-acetate (VII),which is nitrated to (VIII) and finally deacetylated as already described.12.The acylation of isosorbide (I) with isobutyric acid (XIII) by means of sulfuric acid in refluxing chlorobenzene/toluene gives isosorbide 2-O-isobutyrate (XIV),which is nitrated with HNO3/H2SO4 to yield isosorbide 2-O-isobutyrate-5-O-nitrate (XV).Finally,this compound is deacylated by means of NaOH in toluene/water.13.The nitration of isosorbide (I) by means of HNO3 in HOAc/Ac2O gives a 3.5/1 mixture of isosorbide-5-O-nitrate and isosorbide 2-O-nitrate that is separated by column chromatography over alumina.14.The nitration of isosorbide (I) with HNO3 in benzene/HOAc/Ac2O,followed by a purification step yields the target isosorbide-5-O-nitrate.
参考文献标题:Process for the preparation of 1,4:3,6-dianhydro-D-glucite 5-nitrate (isosorbide-5-nitrate)
文献作者:Lauer,K.; Kiegel,E.(Boehringer Ingelheim GmbH)
参考来源:DE 3028873; EP 0045076; US 4431829
合成路线:8.The enantioselective monoacetylation of isosorbide (I) by means of vinyl acetate (VI) catalyzed by Pig liver esterase in dichloromethane gives isosorbide 2-O-acetate (VII),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-acetate-5-O-nitrate (VIII).Finally,this compound is deacetylated by means of K2CO3 in methanol.9.The enantioselective monoacylation of isosorbide (I) by means of vinyl butyrate (IX) catalyzed by Chiraclec-BL in THF or Carlsberg subtilisin in tert-butanol gives isosorbide 2-O-butyrate (X),which is nitrated with HNO3 in acetic anhydride to yield isosorbide 2-O-butyrate-5-O-nitrate (XI).Finally,this compound is deacylated by means of K2CO3 in methanol.10.The acylation of isosorbide (I) with acetic anhydride and pyridine gives the diacetate (XII),which is enantioselectively monodeacetylated by means of lipase from Pseudomonas fluorescens in THF to yield isosorbide 2-O-acetate (VII).This compound is then nitrated to (VIII) and finally deacetylated as already described.11.The acylation of isosorbide (I) with HOAc and Ac2O gives (after purification by crystallization) isosorbide 2-O-acetate (VII),which is nitrated to (VIII) and finally deacetylated as already described.12.The acylation of isosorbide (I) with isobutyric acid (XIII) by means of sulfuric acid in refluxing chlorobenzene/toluene gives isosorbide 2-O-isobutyrate (XIV),which is nitrated with HNO3/H2SO4 to yield isosorbide 2-O-isobutyrate-5-O-nitrate (XV).Finally,this compound is deacylated by means of NaOH in toluene/water.13.The nitration of isosorbide (I) by means of HNO3 in HOAc/Ac2O gives a 3.5/1 mixture of isosorbide-5-O-nitrate and isosorbide 2-O-nitrate that is separated by column chromatography over alumina.14.The nitration of isosorbide (I) with HNO3 in benzene/HOAc/Ac2O,followed by a purification step yields the target isosorbide-5-O-nitrate.
参考文献标题:Process for the preparation of 5-isosorbide nitrate
文献作者:Sch鰊afinger,K.(Cassella AG)
参考来源:DE 3117612; EP 0064194; US 4431830
产品链接: CAS No. 16051-77-7››