【结 构 式】 |
【分子编号】51173 【品名】ethyl 4-[(E)-4-[6,6-dimethyl-2-(4-methylphenyl)-1-cyclohexen-1-yl]-3-buten-1-ynyl]benzoate 【CA登记号】 |
【 分 子 式 】C28H30O2 【 分 子 量 】398.545 【元素组成】C 84.38% H 7.59% O 8.03% |
合成路线1
该中间体在本合成路线中的序号:(XIV)Iodination of 3-methylcyclohexenone (I) using iodine and azidotrimethylsilane produced the iodo ketone (II) (1). Palladium-catalyzed coupling of iodide (II) with 2-(tributylstannyl)ethenyltrimethylsilane (III), prepared from (trimethylsilyl)acetylene and tributyltin hydride, furnished the silylethenyl cyclohexenone (IV), which was further treated with iodine to yield vinyl iodide (V) (1,2). Ethyl 4-ethynylbenzoate (VIII) was prepared by reaction of ethyl 4-iodobenzoate (VI) with (trimethylsilyl)acetylene (VII) in the presence of palladium catalyst (1). Heck reaction between acetylene (VIII) and vinyl iodide (V) provided adduct (IX). Conjugate addition of the in situ generated lithium dimethylcuprate to the unsaturated ketone (IX) gave the 3,3-dimethyl cyclohexanone (X). Treatment of (X) with triflic anhydride and a hindered base produced the desired vinyl triflate (XI) along with its vinyl regioisomer, which were separated by preparative chromatography. Reaction of triflate (XI) with 4-tolylzinc bromide (XIII), prepared from 4-iodotoluene (XII), yielded the phenylcyclohexene derivative (XIV). The ethyl ester group of (XIV) was finally hydrolyzed to the corresponding carboxylic acid using NaOH.
【1】 Standeven, A.M.; Escobar, M.; Beard, R.L.; Klein, E.S.; Chandraratna, R.A.S.; Phenylcyclohexene and phenylcyclohexadiene substituted compounds having retinoid antagonist activity. Bioorg Med Chem Lett 2001, 11, 6, 765. |
【2】 Beard, R.L.; Johnson, A.T.; Teng, M.; Vuligonda, V.; Chandraratna, R.A. (Allergan, Inc.); Aryl- and heteroarylcyclohexenyl substd. alkenes having retinoid agonist, antagonist or inverse agonist type biological activity. EP 0970036; JP 2001513113; US 5760276; WO 9839284 . |
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) | 51163 | 3-Methyl-2-cyclohexen-1-one; 3-Methyl-2-cyclohexenone | 1193-18-6 | C7H10O | 详情 | 详情 |
(II) | 51164 | 2-iodo-3-methyl-2-cyclohexen-1-one | C7H9IO | 详情 | 详情 | |
(III) | 51165 | trimethyl[(E)-2-(tributylstannyl)ethenyl]silane | C17H38SiSn | 详情 | 详情 | |
(IV) | 51166 | 3-methyl-2-[(E)-2-(trimethylsilyl)ethenyl]-2-cyclohexen-1-one | C12H20OSi | 详情 | 详情 | |
(V) | 51167 | 2-[(E)-2-iodoethenyl]-3-methyl-2-cyclohexen-1-one | C9H11IO | 详情 | 详情 | |
(VI) | 23796 | ethyl 4-iodobenzoate | 51934-41-9 | C9H9IO2 | 详情 | 详情 |
(VII) | 23897 | ethynyl(trimethyl)silane;trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
(VIII) | 51168 | ethyl 4-ethynylbenzoate | C11H10O2 | 详情 | 详情 | |
(IX) | 51169 | ethyl 4-[(E)-4-(2-methyl-6-oxo-1-cyclohexen-1-yl)-3-buten-1-ynyl]benzoate | C20H20O3 | 详情 | 详情 | |
(X) | 51170 | ethyl 4-[(E)-4-(2,2-dimethyl-6-oxocyclohexyl)-3-buten-1-ynyl]benzoate | C21H24O3 | 详情 | 详情 | |
(XI) | 51171 | ethyl 4-[(E)-4-(6,6-dimethyl-2-[[(trifluoromethyl)sulfonyl]oxy]-1-cyclohexen-1-yl)-3-buten-1-ynyl]benzoate | C22H23F3O5S | 详情 | 详情 | |
(XII) | 46620 | 1-iodo-4-methylbenzene | C7H7I | 详情 | 详情 | |
(XIII) | 51172 | bromo(4-methylphenyl)zinc | C7H7BrZn | 详情 | 详情 | |
(XIV) | 51173 | ethyl 4-[(E)-4-[6,6-dimethyl-2-(4-methylphenyl)-1-cyclohexen-1-yl]-3-buten-1-ynyl]benzoate | C28H30O2 | 详情 | 详情 |