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【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%

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:(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
Extended Information