【结 构 式】 |
【分子编号】32752 【品名】ethyl 3-[3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-fluorobenzyl)phenyl]propanoate 【CA登记号】 |
【 分 子 式 】C28H26FNO4 【 分 子 量 】459.5171832 【元素组成】C 73.19% H 5.7% F 4.13% N 3.05% O 13.93% |
合成路线1
该中间体在本合成路线中的序号:(X)The reaction of 3-bromo-5-iodobenzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which by a Friedel-Crafts condensation with fluorobenzene (II) by means of AlCl3 in refluxing dichloromethane yields the benzophenone (IV). The condensation of (IV) with ethyl acrylate (V) by means of palladium acetate and triethylamine in refluxing acetonitrile affords the cinnamic acid derivative (VI), which is condensed with N-vinylphthalimide (VII) by means of palladium acetate and diisopropylamine in refluxing xylene to provide the unsaturated adduct (VIII). The reduction of the carbonyl group of (VIII) with triethylsilane and TFA gives the diphenylmethane derivative (IX), which is hydrogenated with H2 over Pd/C in ethyl acetate to yield the saturated diphenylmethane derivative (X). Elimination of the phthalimido group of (X) with hydrazine affords (XI) with a primary amino group. that is sulfonated with 4-chlorophenylsulfonyl chloride (XII) and triethylamine in THF to provide the sulfonamide (XIII). Finally, the ester group of (XIII) is hydrolyzed with aqueous NaOH.
【1】 Waite, D.C.; Mason, C.P.; A scalable synthesis of the thromboxane receptor antagonist 3-(3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl]propionic acid via a regioselective heck cross-coupling strategy. Org Process Res Dev 1998, 2, 2, 116. |
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) | 32745 | 3-bromo-5-iodobenzoic acid | 188815-32-9 | C7H4BrIO2 | 详情 | 详情 |
(II) | 32746 | 3-bromo-5-iodobenzoyl chloride | C7H3BrClIO | 详情 | 详情 | |
(III) | 17466 | Fluorobenzene | 462-06-6 | C6H5F | 详情 | 详情 |
(IV) | 32747 | (3-bromo-5-iodophenyl)(4-fluorophenyl)methanone | C13H7BrFIO | 详情 | 详情 | |
(V) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
(VI) | 32748 | ethyl (E)-3-[3-bromo-5-(4-fluorobenzoyl)phenyl]-2-propenoate | C18H14BrFO3 | 详情 | 详情 | |
(VII) | 32749 | 2-vinyl-1H-isoindole-1,3(2H)-dione | 3485-84-5 | C10H7NO2 | 详情 | 详情 |
(VIII) | 32750 | ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzoyl)phenyl]-2-propenoate | C28H20FNO5 | 详情 | 详情 | |
(IX) | 32751 | ethyl (E)-3-[3-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-5-(4-fluorobenzyl)phenyl]-2-propenoate | C28H22FNO4 | 详情 | 详情 | |
(X) | 32752 | ethyl 3-[3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-fluorobenzyl)phenyl]propanoate | C28H26FNO4 | 详情 | 详情 | |
(XI) | 27001 | ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propanoate | C20H24FNO2 | 详情 | 详情 | |
(XII) | 15787 | 4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride | 98-60-2 | C6H4Cl2O2S | 详情 | 详情 |
(XIII) | 27002 | ethyl 3-[3-(2-[[(4-chlorophenyl)sulfonyl]amino]ethyl)-5-(4-fluorobenzyl)phenyl]propanoate | C26H27ClFNO4S | 详情 | 详情 |