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1、药物详细合成路线NamePhenylephrine hydrochloride;SLV-325;Incostop;Neo-Synephrine hydrochloride;Nostril;Mydfrin;Biomydrin;Alcon EfrinChemical Name(-)-3-1(R)-Hydroxy-2-(methylamino)ethylphenol hydrochlorideCAS 61-76-7Related CAS 59-42-7 (free base)Formula C9H14ClNO2StructureFormula Weight203.67043TelE-mail027-
2、81302267 18007166089 Mr YCompany 武汉东康源科技有限公司Activity/MechanismAnorectal Disorders, Treatment of, GASTROINTESTINAL DRUGSSyn. Route 1Route 13-hydroxybenzaldehyde (i) was protected as the methoxyethoxymethyl ether derivative (ii) by treatment with methoxyethoxymethyl chloride and diisopropyl ethyl amin
3、e. subsequent condensation of (ii) with dimethyloxosulfonium methylide, generated from oxosulfonium salt (iii) and nah, gave rise to the racemic epoxide (iv). kinetic resolution by hydrolysis with (r,r)-n,n-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (iii) acetate complex provide
4、d the (s)-diol (v) along with the unreacted (r)-epoxide (vi), which were separated by column chromatography. opening of the desired (r)-epoxide (vi) with methanolic methylamine gave amino alcohol (vii). finally, removal of the methoxyethoxymethyl group by refluxing in methanolic hcl furnished the ti
5、tle compound.List of intermediatesNo.benzhydryl (7r)-7-amino-3-methyl(dimethylene)-lambda(6)-sulfanyloxy-8-oxo-5-thia-1-azabicyclo4.2.0oct-2-ene-2-carboxylate5,8-dimethyl-2h-chromene-3-carbaldehyde(i)benzhydryl (2r)-3-(acetoxy)methyl-8-oxo-7-(z)-2-pyridinylmethylidene-5-thia-1- (azabicyclo4.2.0oct-3
6、-ene-2-carboxylate iii)(4s,7r,8s,9s)-4-tert-butyl(dimethyl)silyloxy-8-hydroxy-5,5,7,9-tetramethyl-12-(2r,3s)-2-methyl-3-(2s,3e)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-(triethylsilyl)oxy-3-butenyloxiranyl)-1-dodecen-6-one(ii)(1s,2r,5s)-5-tert-butyl(dimethyl)silyloxy-2,4,4-trimethyl-1-(1s)-1-methyl-
7、4-(2r,3s)-2-methyl-3-(2s,3e)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-(triethylsilyl)oxy-3-butenyloxiranyl)butyl-3-oxo-7-octenyl 2,2,2-trichloroethyl carbonate(iv)(3s,6r,7s,8s)-3-tert-butyl(dimethyl)silyloxy-4,4,6,8-tetramethyl-11-(2r,3s)-2-methyl-3-(2s,3e)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-(
8、triethylsilyl)oxy-3-butenyloxiranyl)-5-oxo-7-(2,2,2-trichloroethoxy)carbonyloxyundecanoic acid(v)(3s,6r,7s,8s)-3-tert-butyl(dimethyl)silyloxy-11-(2r,3s)-3-(2s,3e)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl-2-methyloxiranyl-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxy)carbonylox
9、yundecanoic acid(vi)(1s,3s,7s,10r,11s,12s,16r)-7-tert-butyl(dimethyl)silyloxy-8,8,10,12,16-pentamethyl-3-(e)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl-5,9-dioxo-4,17-dioxabicyclo14.1.0heptadec-11-yl 2,2,2-trichloroethyl carbonate(vii)2-(hydroxyamino)-2-methylpropane; n-(tert-butyl)hydroxylamineReference 1:gurjar, m.k.; et al.; a practical synthesis of (r)-(-)-phenylephrine hydrochloride. org process res dev 1998, 2, 6, 422.
