鹽酸去氧腎上腺素 [CAS61-76-7] 合成路線圖解——原料藥廠家武漢東康源

1、.藥物詳細(xì)合成路線NamePhenylephrine hydrochloride;SLV-325;Incostop;Neo-Synephrine hydrochloride;Nostril;Mydfrin;Biomydrin;Alcon EfrinChemical Name(-)-3-1(R)-Hydroxy-2-(methylamino)ethylphenol hydrochlorideCAS61-76-7Related CAS59-42-7 (free base)FormulaC9H14ClNO2StructureFormula Weight203.67043TelE-mail027-81

2、302267Mr YuanchemCompany武漢東康源科技有限公司Activity/MechanismAnorectal Disorders, Treatment of, GASTROINTESTINAL DRUGSSyn. Route1Route 13-hydroxybenzaldehyde (i) was protected as the methoxyethoxymethyl ether derivative (ii) by treatment with methoxyethoxymethyl chloride and diisopropyl ethyl a

3、mine. 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 prov

4、ided 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

5、 title 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-

6、3-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)carbonyloxyundecanoic 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)hydroxy