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【结 构 式】

【分子编号】46261

【品名】N-[(1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]hydroxylamine; (4S)-4-[(1S)-1-(hydroxyamino)-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]-2,2-dimethyl-1,3-dioxolane

【CA登记号】

【 分 子 式 】C20H22F3NO7S

【 分 子 量 】477.4584296

【元素组成】C 50.31% H 4.64% F 11.94% N 2.93% O 23.46% S 6.72%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

The condensation of 4-(trifluoromethoxy)phenol (I) with 4-fluorophenyl(methyl)sulfone (II) by means of K2CO3 in hot DMSO gives the diphenyl ether (III), which is condensed with 2,2-dimethyl-1,3-dioxolane-(R)-carboxylic acid methyl ester (IV) by means of BuLi in THF to afford the ethanone (V). The reduction of (V) with NaBH4 in ethanol yields the ethanol derivative (VI), which is dehydrated to the ethylene (VII) by means of MsCl, TEA and NaHCO3. The addition of hydroxylamine to the double bond of (VII) provides the hydroxyamine derivative (VIII) as a diastereomeric mixture that is separated by flash chromatography, affording the desired enantiomer (IX). Finally, this compound is formylated by treatment with 2,2,2-trifluoroethyl formate (X) (obtained by reaction of 2,2,2-trifluoroethanol (XI) with hot formic acid (XII)) in refluxing MTBE.

1 Curtin, M.L.; Wada, C.K.; Holms, J.H.; et al.; Phenoxyphenyl sulfone N-forylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors. J Med Chem 2002, 45, 1, 219.
2 Curtin, M.L.; Davidsen, S.K.; Michaelides, M.R.; Steinman, D.H.; Dai, Y.; Heyman, H.R.; Holmes, J.H. (Abbott Laboratories Inc.); Reverse hydroxamate inhibitors of matrix metalloproteinases. WO 0044739 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 18780 4-(trifluoromethoxy)phenol 828-27-3 C7H5F3O2 详情 详情
(II) 46256 4-fluorophenyl methyl sulfone; (4-fluorophenyl)(methyl)dioxo-lambda(6)-sulfane C7H7FO2S 详情 详情
(III) 46241 methyl(dioxo)[4-[4-(trifluoromethoxy)phenoxy]phenyl]-lambda(6)-sulfane; methyl 4-[4-(trifluoromethoxy)phenoxy]phenyl sulfone C14H11F3O4S 详情 详情
(IV) 20917 methyl (4R)-2,2-dimethyl-1,3-dioxolane-4-carboxylate 52373-72-5 C7H12O4 详情 详情
(V) 46257 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)-1-ethanone C20H19F3O7S 详情 详情
(VI) 46258 (1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)-1-ethanol C20H21F3O7S 详情 详情
(VII) 46259 (Z)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethenyl 4-[4-(trifluoromethoxy)phenoxy]phenyl sulfone; (4S)-2,2-dimethyl-4-[(Z)-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethenyl]-1,3-dioxolane C20H19F3O6S 详情 详情
(VIII) 46260 (4S)-4-[1-(hydroxyamino)-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]-2,2-dimethyl-1,3-dioxolane; N-[1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]hydroxylamine C20H22F3NO7S 详情 详情
(IX) 46261 N-[(1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]hydroxylamine; (4S)-4-[(1S)-1-(hydroxyamino)-2-([4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl)ethyl]-2,2-dimethyl-1,3-dioxolane C20H22F3NO7S 详情 详情
(X) 46245 2,2,2-trifluoroethyl formate C3H3F3O2 详情 详情
(XI) 19483 2,2,2-trifluoro-1-ethanol 75-89-8 C2H3F3O 详情 详情
(XII) 14590 Formic acid 64-18-6 CH2O2 详情 详情
Extended Information