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【结 构 式】 
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【分子编号】29630 【品名】6-bromo-2,2-dimethyl-4-(4-methylphenyl)-4-thiochromanol 【CA登记号】 |
【 分 子 式 】C18H19BrOS 【 分 子 量 】363.31826 【元素组成】C 59.51% H 5.27% Br 21.99% O 4.4% S 8.83% |
合成路线1
该中间体在本合成路线中的序号：(V)Condensation of 4-bromothiophenol (I) with 3,3-dimethylacrylic acid in the presence of piperidine gave acid (II), which was converted to the corresponding acid chloride with (COCl)2 and then cyclized by treatment with SnCl4 to the thiochromanone (III). Addition of 4-tolyllithium (IV) to ketone (III) and further dehydration of the resulting tertiary alcohol (V) upon treatment with p-toluenesulfonic acid produced the benzothiochromene (VI). After lithiation by means of BuLi, quenching with DMF produced aldehyde (VII). Subsequent Horner-Emmons condensation of (VII) with phosphonate (VIII) in the presence of BuLi yielded a mixture of E and Z olefins from which the required isomer (IX) was isolated by chromatography. Cyclization of ketal (IX) by means of SnCl4 produced the naphthothiopyran (X). The ethyl ester group of (X) was finally hydrolyzed with LiOH to yield the title carboxylic acid.
| 【1】 Escobar, M.; Vuligonda, V.; Standeven, A.M.; Chandraratna, R.A.S.; A new class of potent RAR antagonists: Dihydroanthracenyl, benzochromenyl and benzothiochromenyl retinoids. Bioorg Med Chem Lett 1999, 9, 5, 743. |
| 【2】 Johnson, A.T.; Chandraratna, R.A.; Vuligonda, V. (Allergan, Inc.); Benzo[1,2-g]-chrom-3-ene and benzo[1,2-g]-thiochrom-3-ene derivatives. EP 0948478; WO 9825875 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 34677 | 3-methyl-2-butenoic acid | 541-47-9 | C5H8O2 | 详情 | 详情 | |
| (I) | 29626 | 4-bromophenylhydrosulfide; 4-bromobenzenethiol | 106-53-6 | C6H5BrS | 详情 | 详情 |
| (II) | 29627 | 3-[(4-bromophenyl)sulfanyl]-3-methylbutyric acid | C11H13BrO2S | 详情 | 详情 | |
| (III) | 29628 | 6-bromo-2,2-dimethyl-2,3-dihydro-4H-thiochromen-4-one | C11H11BrOS | 详情 | 详情 | |
| (IV) | 29629 | (4-methylphenyl)lithium | C7H7Li | 详情 | 详情 | |
| (V) | 29630 | 6-bromo-2,2-dimethyl-4-(4-methylphenyl)-4-thiochromanol | C18H19BrOS | 详情 | 详情 | |
| (VI) | 29631 | 6-bromo-2,2-dimethyl-4-(4-methylphenyl)-2H-thiochromene | C18H17BrS | 详情 | 详情 | |
| (VII) | 29632 | 2,2-dimethyl-4-(4-methylphenyl)-2H-thiochromene-6-carbaldehyde | C19H18OS | 详情 | 详情 | |
| (VIII) | 29633 | ethyl 4-[1-(diethoxyphosphoryl)-3,3-dimethoxypropyl]benzoate | C18H29O7P | 详情 | 详情 | |
| (IX) | 29634 | ethyl 4-[(E)-1-(2,2-dimethoxyethyl)-2-[2,2-dimethyl-4-(4-methylphenyl)-2H-thiochromen-6-yl]ethenyl]benzoate | C33H36O4S | 详情 | 详情 | |
| (X) | 29635 | ethyl 4-[2,2-dimethyl-4-(4-methylphenyl)-2H-benzo[g]thiochromen-7-yl]benzoate | C31H28O2S | 详情 | 详情 |