【结 构 式】 |
【分子编号】57084 【品名】2-[3,5-bis(trifluoromethyl)phenyl]propanoyl chloride 【CA登记号】 |
【 分 子 式 】C11H7ClF6O 【 分 子 量 】304.6190992 【元素组成】C 43.37% H 2.32% Cl 11.64% F 37.42% O 5.25% |
合成路线1
该中间体在本合成路线中的序号:(VI)Esterification of 3,5-bis(trifluoromethyl)phenylacetic acid (I) by means of methanolic H2SO4 gives methyl ester (II). Aldol condensation of ester (II) with paraformaldehyde in the presence of K2CO3 and tetrabutylammonium iodide leads to the aryl acrylic acid derivative (III), which is further hydrogenated to the arylpropionic analogue (IV) by using Pd/C. Saponification of the methyl ester group of (IV) affords acid (V). This is then activated as the corresponding acid chloride (VI) upon treatment with oxalyl chloride in the presence of a catalytic amount of DMF.
【1】 Elliott, J.M.; Castro Pineiro, J.L.; Swain, C.J.; Hollingworth, G.J.; Dinnell, K.; Shaw, D.E. (Merck Sharp & Dohme Ltd.); Cyclohexane derivs. and their use as therapeutic agents. WO 0187838 . |
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) | 57079 | 3,5-Bis(trifluoromethyl)phenylacetic acid | 85068-33-3 | C10H6F6O2 | 详情 | 详情 |
(II) | 57080 | methyl 2-[3,5-bis(trifluoromethyl)phenyl]acetate | C11H8F6O2 | 详情 | 详情 | |
(III) | 57081 | methyl 2-[3,5-bis(trifluoromethyl)phenyl]acrylate | C12H8F6O2 | 详情 | 详情 | |
(IV) | 57082 | methyl 2-[3,5-bis(trifluoromethyl)phenyl]propanoate | C12H10F6O2 | 详情 | 详情 | |
(V) | 57083 | 2-[3,5-bis(trifluoromethyl)phenyl]propanoic acid | C11H8F6O2 | 详情 | 详情 | |
(VI) | 57084 | 2-[3,5-bis(trifluoromethyl)phenyl]propanoyl chloride | C11H7ClF6O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(VI)Michael addition of methyl acrylate (VIII) to methyl phenylacetate (VII) in the presence of NaH produces the intermediate triester (IX) which, under the reaction conditions, undergoes Dieckmann cyclization to the cyclohexanone diester (X). Hydrolysis and decarboxylation of keto diester (X) leads to keto acid (XI). This is then subjected to Curtius rearrangement in the presence of diphenylphosphoryl azide (DPPA) to yield, after acidic hydrolysis of the intermediate isocyanate, the amino cyclohexanone (XII). Acylation of amine (XII) by acid chloride (VI) then gives amide (XIII).
【1】 Elliott, J.M.; Castro Pineiro, J.L.; Swain, C.J.; Hollingworth, G.J.; Dinnell, K.; Shaw, D.E. (Merck Sharp & Dohme Ltd.); Cyclohexane derivs. and their use as therapeutic agents. WO 0187838 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 57084 | 2-[3,5-bis(trifluoromethyl)phenyl]propanoyl chloride | C11H7ClF6O | 详情 | 详情 | |
(VII) | 32831 | methyl 2-phenylacetate | 101-41-7 | C9H10O2 | 详情 | 详情 |
(VIII) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
(IX) | 57085 | trimethyl 3-phenyl-1,3,5-pentanetricarboxylate | C17H22O6 | 详情 | 详情 | |
(X) | 57086 | dimethyl 4-oxo-1-phenyl-1,3-cyclohexanedicarboxylate | C16H18O5 | 详情 | 详情 | |
(XI) | 57087 | 4-oxo-1-phenylcyclohexanecarboxylic acid | C13H14O3 | 详情 | 详情 | |
(XII) | 57088 | 4-amino-4-phenylcyclohexanone | C12H15NO | 详情 | 详情 | |
(XIII) | 57089 | 2-[3,5-bis(trifluoromethyl)phenyl]-N-(4-oxo-1-phenylcyclohexyl)propanamide | C23H21F6NO2 | 详情 | 详情 |