233010。L-、、、。L-48.0%。。OptimizationofsynthesisofLevetiracetamWANGHong-huWEIYa-fengCHENWen-jieBengbuBBCAMedicineScience&DevelopmentCo.Ltd.BengbuAnhui233010ChinaAbstractAimToexploretheoptimizationedsyntheticrouteforLevetiracetam.MethodsLevetiracetamwaspreparedfromL-methio-nineviareduction-dethiomethylationesterificationammonolysisamidationandintramolecularcyclocondensaionreaction.ResultsTheoverallyieldwas48.0%calculatedfromL-methionine.ConclusionThereactionyieldwashihgernostrictreactionconditionssimpli-fiedrouteandmoresutabletobeindustrilialized.Keywordslevetiracetamsynthesisoptimization。1~3。UCB、、、、。。42-α-±-α--2--1-R+-α-、。、、5。6~8L-40%。。。L-。2。211。1·186·AnhuiMedicalandPharmaceuticalJournal2011Jun15622.1L-20091022Bchi5101H400.13MHzBruckAM-400PerkinElmer-34l589nm。2.22.2.1S-ⅡL-50g336mmoL4LT-1500g。75~80℃4h。1%8-CHCl32×1000mlCHCl33×1200ml。32.0g98.9%95.0%273~275℃。2.2.2S-ⅢS-25.76g230mmol150ml-10℃37.0ml5h400mlpH=5.5~6.065℃。36.8g99.2%HPLC95.2%148~149℃。1HNMRppm1.02tJ=7.5Hz3H、1.94m2H、3.82s3H、4.00tJ=6.2Hz1H。2.2.3S-2-ⅣS-18.44g120mmol40ml12.12g120mmolHCl450ml。100ml12.0g。100ml5℃2h10ml10h。9.6g78.0%。1HNMRppm1.02tJ=7.2Hz3H、1.95m2H、4.02m1H。2.2.4S-2-2--1-ⅠS-2-9.16g89.8mmol100mlKOH13.44g240mmol1.0g。-5℃16ml31.25g207mmolCH2Cl26hKOH4.0g3h25ml9.34g68.0%116~117℃。C=1。1HNMRppm0.95tJ=7.5Hz3H、1.70m1H、2.04mJ=3.0Hz2H、2.44m1H、3.45m2H、4.44qJ=5.5Hz1H、5.52s1H、6.33s1H。IRKBr3385cm-1NH1676cm-1C=O1618cm-1C=O。33.1S-L-。500gNaBH4/NiCl2·6H2O、W-2T-150gL-75-80℃4hS-T-195.0%W-292.0%NaBH4/NiCl2·6H2O89.5%。3.2S-5。。6PH。99.2%。3.3。。10%V/V。。。2.2.33。3315℃。5℃。。4L-T-1L-95.0%。S-99.2%。10%。5℃3%。L-48.0%。1Kasteleijn-NolstTrenitDGAMarescauxCStodieckSetal.Pho-tosensitiveepilepsyamodeltostudytheeffectsofatlliepiLepticdrugs.EvaluationofthepiracetamanaloguJ.Eveti-racetamEpi-lepsyRes1996253225-30.2.J.201088429-31.·286·AnhuiMedicalandPharmaceuticalJournal2011Jun15611121.2.210029。ZealongaSD4h20h、、、。AP<0.05AP<0.05P>0.05。1h。Erig-eronbreviscapusVanthand-mazz。berviscapineBre1。23。4。。11.1。。0.9%。TTC。。。1.2ACS-HI。JA-1203。DHG-9053A。。1.3SD250~350g。SCXK2009-012。E-mailfangtaihui@sina.com1.4SPSS16.0。LSD。22.12.1.1Zealonga55cm0.285mm20mm。2.1.26~840A1h、B、C、2h、4h、D、E584mg·kg-110ml·kg-1。10%350mg·kg-1ip。0。、Y20mm1.5cm。。4h4。2.22.2.1。4h24h。14021~331~3。10。。2.2.224h3.≤4J.2010191678-80.4SuneesJMarmonVDifferdingEetal.2-Oxo-1-pyrrolidingderiv-ativesprocessforpreparingthemandtheirusesP.WO0164637A12001-09-07.5AtesCSurteesJBurteauA-Cetal.OxopyrrolidineCompoundspreparationofsaidcompoundsandtheiruseinthemanufacturingoflevetiracetamandanaloguesP.WO03014080A22003-02-20.6.J.2004289413-7.7.J.200535227-8.8.J.20071611860-4.2010-12-21·386·AnhuiMedicalandPharmaceuticalJournal2011Jun156