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【结 构 式】 
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【分子编号】35223 【品名】(3S)-3-[(4-bromo-2,6-dimethylphenoxy)methyl]piperidine; 4-bromo-2,6-dimethylphenyl (3S)piperidinylmethyl ether 【CA登记号】 |
【 分 子 式 】C14H20BrNO 【 分 子 量 】298.22294 【元素组成】C 56.39% H 6.76% Br 26.79% N 4.7% O 5.36% |
合成路线1
该中间体在本合成路线中的序号：(VII)Racemic ethyl 3-piperidinecarboxylate (Ia, Ib) was resolved with D-(-)-tartaric acid in EtOH to afford the (S)-piperidine tartrate salt (II). After protection of (II) as the N-Boc derivative (III) by treatment with di-tert-butyl dicarbonate and NaOH, reduction of the carboxylate group of (III) by means of LiBH4 provided alcohol (IV). Subsequent coupling of (IV) with 4-bromo-2,6-dimethylphenol (V) under Mitsunobu conditions provided ether (VI). The N-Boc protecting group of (VI) was then cleaved employing trifluoroacetic acid to give piperidine (VII). Finally, Eschweiler-Clarke methylation using formaldehyde and formic acid furnished the corresponding N-methyl piperidine, which was isolated after conversion to the hydrochloride salt.
| 【1】 Kojima, N.; Nishino, C. (Shiseido Co. Ltd.); Benzamide deriv., anti-ulcer drug, and antibacterial drug. EP 0869124; JP 1998279570; US 5891890 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Ib) | 12453 | ethyl (3R)hexahydro-3-pyridinecarboxylate | C8H15NO2 | 详情 | 详情 | |
| (Ia),(II) | 35224 | ethyl (3S)-3-piperidinecarboxylate | C8H15NO2 | 详情 | 详情 | |
| (III) | 35220 | 1-(tert-butyl) 3-ethyl (3S)-1,3-piperidinedicarboxylate | C13H23NO4 | 详情 | 详情 | |
| (IV) | 35221 | tert-butyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate | C11H21NO3 | 详情 | 详情 | |
| (V) | 31142 | 4-bromo-2,6-dimethylphenol | 2374-05-2 | C8H9BrO | 详情 | 详情 |
| (VI) | 35222 | tert-butyl (3S)-3-[(4-bromo-2,6-dimethylphenoxy)methyl]-1-piperidinecarboxylate | C19H28BrNO3 | 详情 | 详情 | |
| (VII) | 35223 | (3S)-3-[(4-bromo-2,6-dimethylphenoxy)methyl]piperidine; 4-bromo-2,6-dimethylphenyl (3S)piperidinylmethyl ether | C14H20BrNO | 详情 | 详情 |