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【结 构 式】 
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【分子编号】33918 【品名】4-[(3S,4R)-7-methoxy-2-oxo-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenyl acetate 【CA登记号】 |
【 分 子 式 】C24H20O5 【 分 子 量 】388.4198 【元素组成】C 74.21% H 5.19% O 20.6% |
合成路线1
该中间体在本合成路线中的序号：(I)The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II), which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III). This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF. The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V), which is finally isomerized with n-butyllithium in DMSO.
| 【1】 Bolger, J.W.; Process for preparation of substituted 3,4-(diphenyl)chromans. US 3822287 . |
| 【2】 Bolger, J.W.; Procede de preparation de 3,4-(diphenyl)-chromanes substitues. DE 2329201; FR 2187777 . |
| 【3】 Suprabhat, R.; et al.; Antifertility agents. 12. Structure-activity relationship of 3,4-diphenylchromenes and -chromans. J Med Chem 1976, 19, 2, 276-279. |
| 【4】 Castaner, J.; Hillier, K.; Centchroman. Drugs Fut 1977, 2, 7, 441. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 20225 | iodo(methyl)magnesium | 917-64-6 | CH3IMg | 详情 | 详情 |
| (B) | 33922 | 1-(2-Chloroethyl)pyrrolidine; N-(2-Chloroethyl)pyrrolidine | C6H12ClN | 详情 | 详情 | |
| (I) | 33918 | 4-[(3S,4R)-7-methoxy-2-oxo-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenyl acetate | C24H20O5 | 详情 | 详情 | |
| (II) | 33919 | 2-[(1R,2S)-3-hydroxy-1-(4-hydroxyphenyl)-3-methyl-2-phenylbutyl]-5-methoxyphenol | C24H26O4 | 详情 | 详情 | |
| (III) | 33920 | 4-[(3S,4R)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenol | C24H24O3 | 详情 | 详情 | |
| (IV) | 33921 | 4-(7-methoxy-2,2-dimethyl-3-phenyl-2H-chromen-4-yl)phenol | C24H22O3 | 详情 | 详情 | |
| (V) | 33923 | (3S,4R)-2,2-dimethyl-3-phenyl-4-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-3,4-dihydro-2H-chromen-7-yl methyl ether; 1-(2-[4-[(3S,4R)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenoxy]ethyl)pyrrolidine | C30H35NO3 | 详情 | 详情 |