合成路线:The 3-(isopropylamino)propane-1,2(S)-diol (IV) intermediate has been obtained by two different methods:1.The oxidation of 1,2,5,6-O-diisopropylidene-D-mannitol (I) with Pb(OAc)4 in THF gives (R)-2,3-O-isopropylideglyceraldehyde (II),which is reductocondensed with isopropylamine by means of H2 over Pd/C in methanol to yield (S)-3-(isopropylamino)-1,2-O-isopropylidenepropane-1,2-diol (III).The cleavage of the isopropylidene protecting group of (III) in hot 6N HCl affords the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.2.The reductocondensation of (R)-glyceraldehyde (V) with isopropylamine by means of H2 over Pd/C in methanol gives the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.The cyclization of (IV) with benzaldehyde (VI) by heating at 150 C gives the oxazolidine (VII),which is treated with Ts-Cl and K2CO3 in pyridine to yield the tosylate (VIII).Finally,this compound is condensed with 4-[2-(cyclopropylmethoxy)ethyl]phenol (IX) by means of NaH in DMF and hydrolyzed with conc.aq.HCl to provide the target isopropanol derivative.
参考文献标题:S isomer of betaxolol,its preparation and its application in therapy
文献作者:Manoury,P.; Binet,J.(Sanofi-Synthabo)
参考来源:GB 2130585
合成路线:The 3-(isopropylamino)propane-1,2(S)-diol (IV) intermediate has been obtained by two different methods:1.The oxidation of 1,2,5,6-O-diisopropylidene-D-mannitol (I) with Pb(OAc)4 in THF gives (R)-2,3-O-isopropylideglyceraldehyde (II),which is reductocondensed with isopropylamine by means of H2 over Pd/C in methanol to yield (S)-3-(isopropylamino)-1,2-O-isopropylidenepropane-1,2-diol (III).The cleavage of the isopropylidene protecting group of (III) in hot 6N HCl affords the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.2.The reductocondensation of (R)-glyceraldehyde (V) with isopropylamine by means of H2 over Pd/C in methanol gives the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.The cyclization of (IV) with benzaldehyde (VI) by heating at 150 C gives the oxazolidine (VII),which is treated with Ts-Cl and K2CO3 in pyridine to yield the tosylate (VIII).Finally,this compound is condensed with 4-[2-(cyclopropylmethoxy)ethyl]phenol (IX) by means of NaH in DMF and hydrolyzed with conc.aq.HCl to provide the target isopropanol derivative.
参考文献标题:Synthesis of a series of compounds related to betaxolol,a new beta1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases
文献作者:Manoury,P.M.; Binet,J.L.; Rousseau,J.F.; Lefevre-Borg,F.; Cavero,I.G.
参考来源:J Med Chem 1987,30(6),1003-11
合成路线:The condensation of 4-[2-(cyclopropylmethoxy)ethyl]phenol (I) with epichlorohydrin (II) in pyridine gives the phenol ether (III),which is treated with HCl to open the epoxide ring and yield the racemic chloropropanol (IV).The optical resolution of (IV) by means of Lipase SP 435-L or AK and vinyl acetate (V) gives a mixture of (S)-acetate (S)-(VI) and unreacted (R)-alcohol (R)-(VI) that is easily separated.Finally,the chiral chloropropanol (R)-(VI) is treated with isopropylamine (VII) to afford the target betaxolol.The optical resolution of racemic betaxolol by means of the previously mentioned lipases has also been tried with poor results.
参考文献标题:
文献作者:Di Bono,G.; Scilimati,A.
参考来源:Synthesis 1995,(6),688
合成路线:The 3-(isopropylamino)propane-1,2(S)-diol (IV) intermediate has been obtained by two different methods:1.The oxidation of 1,2,5,6-O-diisopropylidene-D-mannitol (I) with Pb(OAc)4 in THF gives (R)-2,3-O-isopropylideglyceraldehyde (II),which is reductocondensed with isopropylamine by means of H2 over Pd/C in methanol to yield (S)-3-(isopropylamino)-1,2-O-isopropylidenepropane-1,2-diol (III).The cleavage of the isopropylidene protecting group of (III) in hot 6N HCl affords the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.2.The reductocondensation of (R)-glyceraldehyde (V) with isopropylamine by means of H2 over Pd/C in methanol gives the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.The cyclization of (IV) with benzaldehyde (VI) by heating at 150 C gives the oxazolidine (VII),which is treated with Ts-Cl and K2CO3 in pyridine to yield the tosylate (VIII).Finally,this compound is condensed with 4-[2-(cyclopropylmethoxy)ethyl]phenol (IX) by means of NaH in DMF and hydrolyzed with conc.aq.HCl to provide the target isopropanol derivative.
参考文献标题:
文献作者:Weinstock,L.M.; et al.
参考来源:J Org Chem 1976,41(19),3121
合成路线:The 3-(isopropylamino)propane-1,2(S)-diol (IV) intermediate has been obtained by two different methods:1.The oxidation of 1,2,5,6-O-diisopropylidene-D-mannitol (I) with Pb(OAc)4 in THF gives (R)-2,3-O-isopropylideglyceraldehyde (II),which is reductocondensed with isopropylamine by means of H2 over Pd/C in methanol to yield (S)-3-(isopropylamino)-1,2-O-isopropylidenepropane-1,2-diol (III).The cleavage of the isopropylidene protecting group of (III) in hot 6N HCl affords the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.2.The reductocondensation of (R)-glyceraldehyde (V) with isopropylamine by means of H2 over Pd/C in methanol gives the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate.The cyclization of (IV) with benzaldehyde (VI) by heating at 150 C gives the oxazolidine (VII),which is treated with Ts-Cl and K2CO3 in pyridine to yield the tosylate (VIII).Finally,this compound is condensed with 4-[2-(cyclopropylmethoxy)ethyl]phenol (IX) by means of NaH in DMF and hydrolyzed with conc.aq.HCl to provide the target isopropanol derivative.
参考文献标题:
文献作者:Baldwin,J.J.; et al.
参考来源:J Med Chem 1979,22(11),1284
产品链接: CAS No. 116209-55-3››