合成路线:In the original synthesis of the title compound,Knoevenagel condensation of benzaldehyde (I) with malonic acid (II) in the presence of ammonium acetate produced the beta-aminoacid (III).Reductive alkylation of the amino group of (III) with formaldehyde produced the dimethyl amine (IV).Then,Fischer esterification of (IV) with ethanolic HCl furnished the intermediate amino ester (V).Amino ester (V) was alternatively obtained by Michael addition of dimethylamine to ethyl cinnamate (VI).Reduction of the ester function of (V) provided amino alcohol (VII).The sodium alkoxide of (VII) was then coupled with 1-fluoronaphthalene (VIII) to produce the racemic amino ether,which was finally resolved into enantiomers by means of tartaric acid.
合成路线:An alternative synthesis starting from the chiral precursor N-Boc-(R)-phenylglycine (IX) was reported.Borane reduction of (IX) provided the N-Boc aminoalcohol (X),which was activated as the mesylate (XI) by reaction with methanesulfonyl chloride in pyridine,yielding (XI).Displacement of the mesylate group of (XI) with NaCN furnished the Boc-aminonitrile (XII).Hydrolysis of the nitrile group of (XII) with concomitant N-Boc group cleavage under acidic conditions gave aminoacid (XIII).This was reduced to amino alcohol (XIV) using borane in THF.Eschweiler-Clarke methylation of aminoalcohol (XIV) yielded the dimethyl amine (XV).This was finally condensed with 1-fluoronaphthalene (VIII) to produce the title naphthyl ether.The [14C]-labeled compound was similarly prepared employing 14C-sodium cyanide.
参考文献标题:A chiral synthesis of dapoxetine hydrochloride,a serotonin reuptake inhibitor,and its 14C isotopomer
文献作者:Wheeler,W.J.; O'Bannon,D.D.
参考来源:J Label Compd Radiopharm 1992,31(4),305
合成路线:The synthesis of the [11C]-labeled compound was also reported.Selective tosylation of the primary hydroxyl of (R)-1-phenyl-1,3-propanediol (XVI) provided (XVII).From this,naphthyl ether (XIX) was prepared by Williamson's synthesis with the sodium alkoxide of 1-naphthol (XVIII).The remaining hydroxyl group of (XIX) was then converted to mesylate (XX) upon treatment with methanesulfonyl chloride and DMAP.Subsequent displacement with methylamine in a sealed vessel afforded the secondary amine (XXI).This was finally alkylated with 11CH3I to yield the target 11C-labeled compound.
参考文献标题:Synthesis of [11C]dapoxetine.HCl,a serotonin re-uptake inhibitor: biodistribution in rat and preliminary PET imaging in the monkey
文献作者:Livni,E.; Satterlee,W.; Robey,R.L.; Alt,C.A.; Van Meter,E.E.; Babich,J.W.; Wheeler,W.J.; O'Bannon,D.D.; Thrall,J.H.; Fischman,A.J.
参考来源:Nucl Med Biol 1994,21(4),669
产品链接: CAS No. 119356-77-3›› 产品链接: CAS No.129938-20-1››