【结 构 式】 |
【分子编号】41091 【品名】methyl 4-[4-(5,5,6,6,6-pentafluorohexanimidoyl)phenyl]butanoate 【CA登记号】 |
【 分 子 式 】C17H20F5NO3 【 分 子 量 】381.342756 【元素组成】C 53.54% H 5.29% F 24.91% N 3.67% O 12.59% |
合成路线1
该中间体在本合成路线中的序号:(IV)Friedel-Crafts acylation of methyl 4-phenylbutyrate (I) with 5,5,6,6,6-pentafluorohexanoyl chloride (II) in the presence of AlCl3 produced ketone (III). This was converted to oxime (IV) upon treatment with hydroxylamine hydrochloride and pyridine, and subsequently reduced to amine (V) by catalytic hydrogenation over Raney nickel. Alternatively, ketone (III) was reduced to alcohol (VI) employing NaBH4. Chlorination of (VI) with SOCl2, followed by displacement with NaN3 furnished azide (VII). Then, reduction of the azido group of (VII) by means of PPh3 provided an alternative route to amine (V). Acylation of amine (V) with 4-fluorobenzenesulfonyl chloride (VIII) gave rise to sulfonamide (IX). The methyl ester group of (IX) was finally hydrolyzed with NaOH yielding the title carboxylic acid.
【1】 Yasuda, S.; Ogawa, N.; Sakurai, S. (Hokuriku Seiyaku Co., Ltd.); Benzenesulfonamide derivs. and drugs containing the same. EP 0943606; JP 1998195038; WO 9821177 . |
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) | 41088 | methyl 4-phenylbutanoate | 2046-17-5 | C11H14O2 | 详情 | 详情 |
(II) | 41089 | 5,5,6,6,6-pentafluorohexanoyl chloride | C6H6ClF5O | 详情 | 详情 | |
(III) | 41090 | methyl 4-[4-(5,5,6,6,6-pentafluorohexanoyl)phenyl]butanoate | C17H19F5O3 | 详情 | 详情 | |
(IV) | 41091 | methyl 4-[4-(5,5,6,6,6-pentafluorohexanimidoyl)phenyl]butanoate | C17H20F5NO3 | 详情 | 详情 | |
(V) | 41092 | methyl 4-[4-(1-amino-5,5,6,6,6-pentafluorohexyl)phenyl]butanoate | C17H22F5NO2 | 详情 | 详情 | |
(VI) | 41093 | methyl 4-[4-(5,5,6,6,6-pentafluoro-1-hydroxyhexyl)phenyl]butanoate | C17H21F5O3 | 详情 | 详情 | |
(VII) | 41094 | methyl 4-[4-(1-azido-5,5,6,6,6-pentafluorohexyl)phenyl]butanoate | C17H20F5N3O2 | 详情 | 详情 | |
(VIII) | 12292 | 4-Fluorobenzenesulfonyl chloride | 349-88-2 | C6H4ClFO2S | 详情 | 详情 |
(IX) | 41094 | methyl 4-[4-(1-azido-5,5,6,6,6-pentafluorohexyl)phenyl]butanoate | C17H20F5N3O2 | 详情 | 详情 |