【结 构 式】 |
【分子编号】12844 【品名】(4-Iodophenyl)lithium 【CA登记号】 |
【 分 子 式 】C6H4ILi 【 分 子 量 】209.94323 【元素组成】C 34.33% H 1.92% I 60.45% Li 3.31% |
合成路线1
该中间体在本合成路线中的序号:(B)Initially, a small-scale synthetic route to idoxifene had been described involving Friedel-Crafts acylation of 2-chloroethoxybenzene by 2-phenylbutyric acid followed by reaction of the resulting ketone with 4-iodophenyllithium (prepared by monolithiation of 1,4-diiodobenzene) . A mixture of E and Z isomers of the triphenylbutene was then produced by dehydration of the intermediate tertiary alcohol from which the desired E isomer (in which the unsubstituted phenyl and iodophenyl residues are in a trans relationship) was separated by crystallization. Idoxifene was then produced by final modification of the chloroethoxy side chain using pyrrolidine. Modification of the above scheme to provide an efficient, large-scale synthesis of idoxifene has now been described initially involving treatment of 2-phenoxyethanol with pyridine (in catalytic amounts) and thionyl chloride/heat to produce 2-chloroethoxybenzene.
【1】 Kelland, L.R.; Jarman, M.; Idoxifene. Drugs Fut 1995, 20, 7, 666. |
【2】 Potter, G.A.; Jarman, M.; McCague, R.; An efficient, large-scale synthesis of idoxifene ((E)-1-[4-[N-(pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene). Org Prep Proced Int 1994, 26, 343-6. |
【3】 McCague, R. (National Research Development Corp.); Tamoxifen derivs. EP 0260066; GB 2196003; JP 1988077845 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 12844 | (4-Iodophenyl)lithium | C6H4ILi | 详情 | 详情 | |
(A) | 21130 | 2-Phenylbutyric acid; alpha-Ethylbenzeneacetic acid | 90-27-7 | C10H12O2 | 详情 | 详情 |
(I) | 12841 | 2-Phenoxyethanol; 2-Phenoxy-1-ethanol | 122-99-6 | C8H10O2 | 详情 | 详情 |
(II) | 12842 | 2-Chloroethyl phenyl ether; b-Chlorophenetole; 1-(2-Chloroethoxy)benzene | 622-86-6 | C8H9ClO | 详情 | 详情 |
(III) | 12843 | 1-[4-(2-Chloroethoxy)phenyl]-2-phenyl-1-butanone | C18H19ClO2 | 详情 | 详情 | |
(IV) | 12845 | 2-Chloroethyl 4-[(E)-1-(4-iodophenyl)-2-phenyl-1-butenyl]phenyl ether; 1-[(E)-1-[4-(2-Chloroethoxy)phenyl]-2-phenyl-1-butenyl]-4-iodobenzene | C24H22ClIO | 详情 | 详情 | |
(V) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |