【结 构 式】 |
【分子编号】34138 【品名】(1S,3S)-3-(4-fluorophenyl)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-ol 【CA登记号】 |
【 分 子 式 】C16H12F4O 【 分 子 量 】296.2642928 【元素组成】C 64.87% H 4.08% F 25.65% O 5.4% |
合成路线1
该中间体在本合成路线中的序号:(XIb)The Sandmeyer reaction of 4-trifluoromethylanthranilic acid (I) with NaNO2, HBr and Cu2Br2 gives 2-bromo-4-trifluoromethylbenzoic acid (II), which by reaction with SOCl2 is converted into 2-bromo-4-trifluoromethylbenzoyl chloride (III). The Rosemind reduction of (III) with H2 over Pd/BaSO4/S yields 2-bromo-4-trifluoromethylbenzaldehyde (IV), which is condensed with ethyl cyanacetate (V) in refluxing toluene affording ethyl 2-cyano-3-[2-bromo-4-(trifluoromethyl)phenyl]propenoate (VI). The addition of 4-fluorophenylmagnesium bromide (VII) to (VI) in toluene ether gives ethyl 2-cyano-3-[2-bromo-4-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)propanoate (VIII), which is hydrolyzed and decarboxylated partially with H2SO4 in refluxing acetic acid water to yield 3-[2-bromo-4-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)propanoic acid (IX). Cyclization of (IX) with butyllithium in ether affords 3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-one (X), which is reducted with NaBH4 in methanol giving 3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-ol (XI). The reaction of (XI) with SOCl2 in hot toluene yields 1-chloro-3-(4-fluorophenyl)-6-(trifluoromethyl)indan (XII).
【1】 Castaner, J.; Serradell, M.N.; Tefludazine. Drugs Fut 1984, 9, 5, 346. |
【2】 Bogeso, K.P.; Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans. J Med Chem 1983, 26, 7, 935-947. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XIa) | 34137 | (1S,3R)-3-(4-fluorophenyl)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-ol | C16H12F4O | 详情 | 详情 | |
(XIb) | 34138 | (1S,3S)-3-(4-fluorophenyl)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-ol | C16H12F4O | 详情 | 详情 | |
(XIIa) | 34139 | (1R,3S)-3-chloro-1-(4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1H-indene | C16H11ClF4 | 详情 | 详情 | |
(XIIb) | 34140 | (1S,3S)-3-chloro-1-(4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1H-indene | C16H11ClF4 | 详情 | 详情 | |
(I) | 34129 | 2-amino-4-(trifluoromethyl)benzoic acid | C8H6F3NO2 | 详情 | 详情 | |
(II) | 34130 | 2-bromo-4-(trifluoromethyl)benzoic acid | C8H4BrF3O2 | 详情 | 详情 | |
(III) | 34131 | 2-bromo-4-(trifluoromethyl)benzoyl chloride | C8H3BrClF3O | 详情 | 详情 | |
(IV) | 34132 | 2-bromo-4-(trifluoromethyl)benzaldehyde | C8H4BrF3O | 详情 | 详情 | |
(V) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
(VI) | 34133 | ethyl (Z)-3-[2-bromo-4-(trifluoromethyl)phenyl]-2-cyano-2-propenoate | C13H9BrF3NO2 | 详情 | 详情 | |
(VII) | 13643 | 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide | 352-13-6 | C6H4BrFMg | 详情 | 详情 |
(VIII) | 34134 | ethyl 3-[2-bromo-4-(trifluoromethyl)phenyl]-2-cyano-3-(4-fluorophenyl)propanoate | C19H14BrF4NO2 | 详情 | 详情 | |
(IX) | 34135 | 3-[2-bromo-4-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)propionic acid | C16H11BrF4O2 | 详情 | 详情 | |
(X) | 34136 | 3-(4-fluorophenyl)-6-(trifluoromethyl)-1-indanone | C16H10F4O | 详情 | 详情 |