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【结 构 式】 
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【分子编号】44835 【品名】(1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid 【CA登记号】 |
【 分 子 式 】C15H18ClNO2 【 分 子 量 】279.76616 【元素组成】C 64.4% H 6.49% Cl 12.67% N 5.01% O 11.44% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Treatment of (S)-glycidol (I) with triphenylmethyl chloride (Ph3CCl) in pyridine affords O-triphenylmethylglicydyl ether (II), which is then reduced with LiAlH4 in THF to provide alcohol (III). Hydrogenolysis of (III) over Pd/C in MeOH gives 1,2-propandiol (IV), which is then mesylated by means of methanesulfonyl chloride (MsCl) and Et3N in CH2Cl2 to furnish 1-mesyloxy-2-propanol (V). Treatment of tropane (VI) with a refluxing mixture of dioxane/H2O yields carboxylic acid (VII), which is converted into acid chloride (VIII) by means of phosphorus oxychloride (POCl3). Coupling of alcohol (V) with acid chloride (VIII) and Et3N in CH2Cl2 gives tropane derivative (IX), which is finally converted into the target compound by fluorination with tetrabutylammonium fluoride (TBAF) in THF.
| 【1】 Xing, D.; Keil, R.; Chen, P.; et al.; Synthesis, biodistribution, and primate imaging of fluorine-18 labeled 2 beta-carbo-1'-fluoro-2-propoxy-3beta-(4-chlorophenyl)tropanes. Ligands for the imaging of dopamine transporters by positron emission tomography. J Med Chem 2000, 43, 4, 639. |
| 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) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (II) | 41006 | (2S)-oxiranylmethyl trityl ether; (2S)-2-[(trityloxy)methyl]oxirane | C22H20O2 | 详情 | 详情 | |
| (III) | 44832 | (2R)-1-(trityloxy)-2-propanol | C22H22O2 | 详情 | 详情 | |
| (IV) | 19242 | (2S)-1,2-propanediol | 4254-15-3 | C3H8O2 | 详情 | 详情 |
| (V) | 44833 | (2R)-1-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-propanol | C6H14O2S | 详情 | 详情 | |
| (VI) | 44837 | (1R)-1-methyl-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | C21H30ClNO3S | 详情 | 详情 | |
| (VII) | 44834 | methyl (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | C16H20ClNO2 | 详情 | 详情 | |
| (VIII) | 44835 | (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid | C15H18ClNO2 | 详情 | 详情 | |
| (IX) | 44836 | (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride | C15H17Cl2NO | 详情 | 详情 |