合成路线:The reaction of 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-one (I) with methylamine by means of TiCl4 in toluene gives the corresponding imine (II),which is reduced with H2 over 5% Pd/graphite,yielding a 12:1 mixture of (??(cis)(III) and (?)(trans)(III).This mixture was resolved by a treatment with (D)-mandelic acid,crystallization of the resulting salt,and treatment with NaOH in toluene/water to afford the target (+)(S,S)(cis)-sertraline.
参考文献标题:Novel process for preparing (+)-cis-sertraline
文献作者:Gershon,N.; Nidam,T.; Mendelovich,M.; Pilarsky,G.(Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA,Inc.)
参考来源:WO 0168566
合成路线:The reaction of 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-one (I) with methylamine and formic acid in DMF gives the corresponding methylimine (II),which is reduced with H2 over Pd/C to yield (rac)(cis)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (rac)(cis)(III).Finally,this compound is submitted to optical resolution by means of mandelic acid to afford the target (1S)(cis)-sertraline.
参考文献标题:Process for the production of sertraline and intermediates useful therefor
文献作者:Laitinen,I.; Pietikaeinen,P.(Orion Corporation)
参考来源:US 2003013768
合成路线:The Friedel-Kraft's reaction of benzene (I) and 3,4-dichlorobenzoyl chloride (II) by means of AlCl3 in dichloromethane gives 3,4-dichlorobenzophenone (III),which is condensed with diethyl succinate (IV) by means of potassium tert-butoxide in tert-butyl alcohol yielding ethyl 3-ethoxycarbonyl-4-(3,4-dichlorophenyl)-4-phenylbut-3-enoate (V).Hydrolysis of (V) with HBr in refluxing acetic acid affords 4-(3,4-dichlorophenyl)-4-phenylbut-3-enoic acid (VI),which is hydrogenated with H2 over Pd/C in ethyl acetate giving 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid (VII),which is converted into the corresponding acyl chloride (VIII) with refluxing SOCl2.Cyclization of (VIII) with AlCl3 in CS2 yields 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (IX),which is treated with methylamine and TiCl4 in THF affording the corresponding Schiff base (X).Finally,this compound is reduced with H2 over Pd/C in THF.
参考文献标题:Sertraline
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1984,9(4),277
合成路线:A new synthesis of [7-3H]-sertraline has been described:The optical resolution of 7-bromo-1-(methylamino)tetraline (I) with N-acetyl-D-phenylalanine gives the (R)-isomer (II),which is acylated with formic acid - acetic anhydride to the formamide (III).The oxidation of (III) with KMnO4 in acetone - water yields 6-bromo-4(R)-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (IV),which,by a Grignard condensation with 3,4-dichlorophenylmagnesium bromide (V) in ether - toluene,affords 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)-1,2,3,4-tetrahydronaphthalen-1-ol (VI).The reduction of (VI) with triethylsilane tetrafluoroborate in dichloromethane gives 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)tetraline (VII),which is hydrolyzed with HCl in isopropanol to the corresponding methylamine (VIII).Oxidation of (VIII) with NaClO NaOCH3 in methanol - water yields the imine (IX),which is reduced with NaBH4 in THF - methanol to 6-bromo-1(S)-(3,4-dichlorophenyl)-4(S)-(methylamino)tetraline (X),along with starting (VIII).After separation by column chromatography,(X) is reduced with H2 over Pd/C or with T2 over Pd/C in THF containing triethylamine.
参考文献标题:Synthesis of 7-3H-(IS,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-I-naphthalenamine hydrochloride (7-3H-sertraline)
文献作者:Williams,M.T.; Welch,W.M.
参考来源:J Label Compd Radiopharm 1993,33(2),119
合成路线:A stereoselective synthesis of sertraline has been described:The silylation of 1,2-dihydronaphthalen-1(R)-ol (I) with tert-butyldiphenylsilyl chloride (TBDPS-Cl) gives the corresponding silyl ether (II),which is brominated with Br2 and triethylamine (TEA) in dichloromethane yielding the 4-bromo-compound (III).The condensation of (III) with 3,4-dichlorophenyltrimethyltin (IV),by means of a palladium catalyst affords the silylated phenylnaphthalenol (V),which is deprotected with TBAF and acetic acid to provide 4-(3,4-dichlorophenyl)-1,2-dihydronaphthalen-1(R)-ol (VI).The regioselective hydrogenation with H2 over chiral iridium or rhodium catalysts gives the (1R-trans)-tetrahydronaphthol (VII),which is treated with diphenylphosphoryl azide (DPPA) and DBU in THF yielding the (1S-cis)-azide (VIII).The reduction of (VIII) with H2 over Pd/C in ethanol affords the corresponding amine (IX),which is treated with ethyl chloroformate to give the expected carbamate (X).Finally,this compound is reduced with LiAlH(OMe)3 in THF.2,4-Dichlorophenyltrimethyltin (IV) is prepared by reaction of 3,4-dichlorophenol (XI) with triflic anhydride in pyridine/CH2Cl2 to give triflate (XII),which is converted to (IV) by reaction with hexamethylditin and Pd(PPh3)4 in THF.The silylated naphthalenol (V) can also be obtained by condensation of (III) with the phenylboronic acid (XIII) in the presence of a palladium catalyst.
参考文献标题:Selective functionalization of 1,2-dihydronaphthalenols leads to a concise,stereoselective synthesis of sertraline
文献作者:Rovis,T.; Lautens,M.
参考来源:Tetrahedron 1999,55(29),8967
合成路线:A new total synthesis of sertraline has been described: The reduction of N,N-dibenzyl-D-phenylglycine methyl ester (I) with LiAlH4 in THF gives alcohol (II),which is oxidized to aldehyde (III) with oxalyl chloride in dichloromethane.The condensation of (III) with the phosphorane (IV) in benzene yields the unsaturated ester (V),which is reduced with Mg in methanol affording the saturated methyl ester (VI).Reduction of (VI) with LiAlH4 in THF provides the corresponding butanol derivative (VII),which is oxidized to the aldehyde (VIII) with pyridinium dichromate (PDC) in dichloromethane.The Grignard reaction of (VIII) with 3,4-dichlorophenylmagnesium bromide (IX) in THF affords the secondary alcohol (X),which is cyclized by means of AlCl3 in dichloromethane yielding a mixture of the desired cis-isomer (XI) along with some trans-isomer separated by column chromatography.Debenzylation of (XI) by H2 over Pd(OH)2 in methanol,followed by protection with Boc2O yields the carbamate (XII),which is methylated with methyl iodide and NaH in THF to afford the protected intermediate (XIII).Finally,compound (XIII) is deprotected with TFA in dichloromethane.
参考文献标题:An expedient total synthesis of cis-(+)-sertraline from D-phenylglycine
文献作者:Chandrasekhar,S.; Reddy,M.V.
参考来源:Tetrahedron 2000,56(8),1111
产品链接: CAS No. 79617-96-2›› 产品链接: CAS No.79559-97-0››