【结 构 式】 |
【分子编号】17181 【品名】2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropanal 【CA登记号】 |
【 分 子 式 】C32H37NO3 【 分 子 量 】483.65072 【元素组成】C 79.47% H 7.71% N 2.9% O 9.92% |
合成路线1
该中间体在本合成路线中的序号:(IX)1) The reduction of 2-methyl-2-phenylpropionic acid with LiAlH4 in THF gives 2-methyl-2-phenyl-1-propanol (II), which is acetylated with acetic anhydride in pyridine yielding the acetate (III). The Friedel-Crafts condensation of (III) with 4-chlorobutyryl chloride (IV) by means of AlCl3 in dichloromethane affords the butyrophenone (V), which is condensed with alpha,alpha-diphenylipiperidine-4-methanol (VI) by means of KHCO3 and KI in refluxing toluene/water to give the butyrophenone (VII). The deacetylation of (VII) with NaOH in refluxing methanol yields the primary alcohol (VIII), which is oxidized with oxalyl chloride and DMSO in methylene chloride to the corresponding aldehyde (IX). The oxidation of (IX) with KMnO4 in acetone affords the ketoacid (X), which is finally reduced with NaBH4 in water. 2) The acetate (III) can also be obtained by Friedel-Crafts condensation of 2-methyl-2-propenyl acetate (XI) with refluxing benzene (XII) by means of AlCl3. 3) The ketoacid (X) can also be obtained by direct oxidation of the primary alcohol (VIII) with H5IO6 in chloroform/acetonitrile, or K2S2O8 in acetone/acetonitrile, both catalyzed by RuCl3.5H2O.
【1】 Graul, A.; Castañer, J.; Fexofenadine Hydrochloride. Drugs Fut 1996, 21, 10, 1017. |
【2】 King, C.-H.; Kaminski, M.A. (Merrell Pharmaceuticals, Inc.); 4-Diphenylmethyl piperidine derivs. and process for their preparation. JP 1996502022; WO 9321156 . |
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) | 17173 | 2-Methyl-2-phenylpropionic acid; 2-Methyl-2-phenyl-propionic acid | 826-55-1 | C10H12O2 | 详情 | 详情 |
(II) | 17174 | 2-methyl-2-phenyl-1-propanol | C10H14O | 详情 | 详情 | |
(III) | 17175 | 2-methyl-2-phenylpropyl acetate | 2901-13-5 | C12H16O2 | 详情 | 详情 |
(IV) | 11265 | 4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride | 4635-59-0 | C4H6Cl2O | 详情 | 详情 |
(V) | 17177 | 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropyl acetate | C16H21ClO3 | 详情 | 详情 | |
(VI) | 17178 | diphenyl(4-piperidinyl)methanol; alpha,alpha-Diphenyl-4-piperidinomethanol; Azacyclonol | 115-46-8 | C18H21NO | 详情 | 详情 |
(VII) | 17179 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropyl acetate | 76811-96-6 | C34H41NO4 | 详情 | 详情 |
(VIII) | 17180 | 1-[4-(2-hydroxy-1,1-dimethylethyl)phenyl]-4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]-1-butanone | C32H39NO3 | 详情 | 详情 | |
(IX) | 17181 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropanal | C32H37NO3 | 详情 | 详情 | |
(X) | 17182 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropionic acid | 76811-98-8 | C32H37NO4 | 详情 | 详情 |
(XI) | 17183 | 2-methyl-2-propenyl acetate;methallyl acetate | 820-71-3 | C6H10O2 | 详情 | 详情 |
(XII) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
(XIV) | 17609 | ethyl 2-methyl-2-phenylpropanoate | C12H16O2 | 详情 | 详情 | |
(XV) | 17610 | ethyl 2-[4-(cyclopropylcarbonyl)phenyl]-2-methylpropanoate | C16H20O3 | 详情 | 详情 | |
(XVI) | 17611 | ethyl 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoate | C16H21ClO3 | 详情 | 详情 | |
(XVII) | 17612 | ethyl 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropanoate | C34H41NO4 | 详情 | 详情 | |
(XVIII) | 17613 | ethyl 2-[4-(1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butyl)phenyl]-2-methylpropanoate | C34H43NO4 | 详情 | 详情 |