合成路线:1) The cyclization of 4-fluorophenol (I) with chronic acid (II) by means of polyphosphonic acid (PPA) at 120 C gives 6-fluoro-2-methyl-chroman-4-one (III),which is then condensed with KCN and ammonium carbonate in hot acetamide.
参考文献标题:Treating complications of diabetes mellitus with hydantoin derivatives
文献作者:Ueda,K.; et al.(Eisai Co.,Ltd.)
参考来源:BE 889698; DE 3128606; FR 2487353; GB 2080304; JP 57045185; US 4780472; US 4874869
合成路线:1) The cyclization of 4-fluorophenol (I) with chronic acid (II) by means of polyphosphonic acid (PPA) at 120 C gives 6-fluoro-2-methyl-chroman-4-one (III),which is then condensed with KCN and ammonium carbonate in hot acetamide.
合成路线:2) The condensation of 4-fluorophenol (I) with ethyl (S)-lactate (II) by means of diethyl azodicarboxylate and triphenylphosphine in THF gives ethyl 2(R)-(4-fluorophenoxy)propionate (III),which is reduced with LiAlH4 in THF yielding 2(R)-(4-fluorophenoxy)propanol (IV).The reaction of (IV) with Br2 and triphenylphosphine in DMF affords 1-bromo-2(R)-(4-fluorophenoxy)propane (V),which is condensed with N-benzoyl-2-hydroxyglycine (VI) by means of methanesulfonic acid to give (RS)-N-benzoyl-2-[2-(1-bromo-2(R)propoxy)-5-fluorophenyl]glycine (VII).The cyclization of (VII) by means of acetic anhydride and K2CO3 in acetone yields 6-fluoro-2(R)-methyl-2'-phenylspiro[2,3-dihydro-4H-1-benzopyran-4(RS),4'-oxazolidin]-5'-one (VIII),which is hydrolyzed with refluxing formic acid-HCl affording 4(RS)-amino-6-fluoro-2(R)-methyl-2,3-dihydro-4H-1-benzopyran-4-carboxylic acid (IX).The esterification of (IX) with Cl2SO and methanol gives the corresponding methyl ester (X),which is submitted to optical resolution with alpha-chymotrypsine to yield methyl 4(S)-amino-6-fluoro-2(R)-methyl-2,3-dihydro-4H-1-benzopyran-4-carboxylate (XI).Finally,this compound is cyclized with sodium cyanate in acetic acid.
参考文献标题:METHOSORBINIL
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(4),325
产品链接: CAS No. 82319-87-7››