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【结 构 式】 
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【分子编号】60053 【品名】2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]-2-oxoacetyl chloride 【CA登记号】 |
【 分 子 式 】C23H19Cl2NO2 【 分 子 量 】412.3148 【元素组成】C 67% H 4.64% Cl 17.2% N 3.4% O 7.76% |
合成路线1
该中间体在本合成路线中的序号：(VII)The cyclization of 4-chloro-3,3-dimethylbutyronitrile (I) with benzylmagnesium chloride (II) in ethyl ether containing some iodine gives 2-benzyl-4,4-dimethyl-1-pyrroline (III), which is cyclized with 4'-chlorophenacyl bromide (IV) by means of NaHCO3 in methanol, yielding 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro.1H-pyrrolizine (V). The condensation of (V) with oxalyl chloride (VI) in THF affords 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]-2-oxoacetyl chloride (VII), which is finally reduced and hydrolyzed with hydrazine in hot diethyleneglycol to provide the target licofelone.
| 【1】 Laufer, S.; Striegel, H.-G.; Kammermeier, T.; Merckle, P. (Merckle GmbH); Method for producing 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl acetic acid. US 6417371; WO 0155149 . |
| 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) | 60052 | 4-chloro-3,3-dimethylbutanenitrile | C6H10ClN | 详情 | 详情 | |
| (II) | 18327 | benzyl(chloro)magnesium | 6921-34-2 | C7H7ClMg | 详情 | 详情 |
| (III) | 16719 | 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole | 116673-95-1 | C13H17N | 详情 | 详情 |
| (IV) | 16720 | 2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone | 536-38-9 | C8H6BrClO | 详情 | 详情 |
| (V) | 16721 | 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine | C21H20ClN | 详情 | 详情 | |
| (VI) | 29841 | Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride | 79-37-8 | C2Cl2O2 | 详情 | 详情 |
| (VII) | 60053 | 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]-2-oxoacetyl chloride | C23H19Cl2NO2 | 详情 | 详情 |