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【结 构 式】 
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【分子编号】36977 【品名】2-[4-bromo-1-(3-methyl-2-thienyl)-1-butenyl]-3-methylthiophene 【CA登记号】 |
【 分 子 式 】C14H15BrS2 【 分 子 量 】327.3091 【元素组成】C 51.37% H 4.62% Br 24.41% S 19.59% |
合成路线1
该中间体在本合成路线中的序号：(VII)This compound has been obtained by two different ways: 1) The Grignard condensation of 3-methylthiophene-2-carbaldehyde (I) with 3-methylthiophen-2-ylmagnesium bromide (II) in ethyl ether gives the carbinol (III), which is oxidized with MnO2 in dichloromethane yielding the corresponding ketone (IV). A new Grignard condensation of (IV) with cyclopropylmagnesium bromide (V) in THF affords the carbinol (VI), which is dehydrated with simultaneous cyclopropane ring opening by means of HBr or TMS-Br in acetic acid giving 4,4-bis(3-methyl-2-thienyl)-3-butenyl bromide (VII).The condensation of (VII) with piperidine-2(R)-carboxylic acid ethyl ester (VIII) by means of K2CO3 and KI in acetone yields the ethyl ester (IX) of the target compound, which is finally hydrolyzed with NaOH in ethanol. 2) The reaction of 2-bromo-3-methylthiophene (X) with BuLi in ethyl ether gives the corresponding lithium derivative (XI), which is condensed with ethyl 4-bromobutyrate (XII) in the same solvent to afford the previously reported 4,4-bis(3-methyl-2-thienyl)-3-butenyl bromide (VII).
| 【1】 Braestrup, C.; Gronvald, F.C. (Novo Nordisk A/S); Amino acid derivs.. AU 8661336; EP 0236342; ES 8800927; JP 1987503172; US 5010090; WO 8700171 . |
| 【2】 Andersen, K.E.; et al.; The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4, 4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate. J Med Chem 1993, 36, 12, 1716. |
| 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) | 12446 | 3-Methyl-2-thiophenecarboxaldehyde; 3-Methyl-2-thiophenecarbaldehyde | 5834-16-2 | C6H6OS | 详情 | 详情 |
| (II) | 36973 | bromo(3-methyl-2-thienyl)magnesium | C5H5BrMgS | 详情 | 详情 | |
| (III) | 36974 | bis(3-methyl-2-thienyl)methanol | C11H12OS2 | 详情 | 详情 | |
| (IV) | 36975 | bis(3-methyl-2-thienyl)methanone | C11H10OS2 | 详情 | 详情 | |
| (V) | 12450 | Bromo(cyclopropyl)magnesium;cyclopropylmagnesium bromide;cyclopropylmagnesiumbromide | 23719-80-4 | C3H5BrMg | 详情 | 详情 |
| (VI) | 36976 | cyclopropyl[bis(3-methyl-2-thienyl)]methanol | C14H16OS2 | 详情 | 详情 | |
| (VII) | 36977 | 2-[4-bromo-1-(3-methyl-2-thienyl)-1-butenyl]-3-methylthiophene | C14H15BrS2 | 详情 | 详情 | |
| (VIII) | 12453 | ethyl (3R)hexahydro-3-pyridinecarboxylate | C8H15NO2 | 详情 | 详情 | |
| (IX) | 36978 | ethyl (3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylate | C22H29NO2S2 | 详情 | 详情 | |
| (X) | 12443 | 2-Bromo-3-methylthiophene | 14282-76-9 | C5H5BrS | 详情 | 详情 |
| (XI) | 36979 | (3-methyl-2-thienyl)lithium | C5H5LiS | 详情 | 详情 | |
| (XII) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |