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【结 构 式】 
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【分子编号】49553 【品名】1-[3-(4-fluorophenoxy)propanoyl]-3-methoxy-4-piperidinone O-benzyloxime 【CA登记号】 |
【 分 子 式 】C22H25FN2O4 【 分 子 量 】400.4499832 【元素组成】C 65.99% H 6.29% F 4.74% N 7% O 15.98% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The condensation of 3-(4-fluorophenoxy)propionic acid (I) with 4-piperidone (II) by means of pivaloyl chloride and TEA in refluxing toluene gives the amide (III), which is submitted to oxidation with diacetoxyiodobenzene and KOH in methanol, yielding the hydroxy-dimethoxyketal (IV). The methylation of the OH group of (IV) with Me-I and Ag2O in DMF affords the corresponding methoxy compound (V), which is hydrolyzed with HOAc to provide the methoxypiperidone (VI). The reaction of (VI) with O-benzylhydroxylamine (VII) and pyridine in refluxing toluene gives the oxime (VIII), which is diastereoselectively reduced with BH3 in THF, yielding the cis-isomer (IX). Finally, this amine is condensed with 4-amino-5-chloro-2-methoxybenzoic acid (X) by means of ethyl chloroformate, TEA and HOBt in DMF to afford the target amide.
| 【1】 Cossy, J.; et al.; A short synthesis of cisapride: A gastrointestinal stimulant derived from cis-4-amino-3-methoxypiperidine. Tetrahedron Lett 2001, 42, 33, 5713. |
| 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) | 39121 | 3-(4-fluorophenoxy)propionic acid | 2967-70-6 | C9H9FO3 | 详情 | 详情 |
| (II) | 27115 | 4-piperidinone | 40064-34-4 | C5H9NO | 详情 | 详情 |
| (III) | 49549 | 1-[3-(4-fluorophenoxy)propanoyl]-4-piperidinone | C14H16FNO3 | 详情 | 详情 | |
| (IV) | 49550 | 3-(4-fluorophenoxy)-1-(3-hydroxy-4,4-dimethoxy-1-piperidinyl)-1-propanone | C16H22FNO5 | 详情 | 详情 | |
| (V) | 49551 | 3-(4-fluorophenoxy)-1-(3,4,4-trimethoxy-1-piperidinyl)-1-propanone | C17H24FNO5 | 详情 | 详情 | |
| (VI) | 49552 | C15H18FNO4 | 详情 | 详情 | ||
| (VII) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (VIII) | 49553 | 1-[3-(4-fluorophenoxy)propanoyl]-3-methoxy-4-piperidinone O-benzyloxime | C22H25FN2O4 | 详情 | 详情 | |
| (IX) | 49554 | (3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinamine; (3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidinylamine | C15H23FN2O2 | 详情 | 详情 | |
| (X) | 12419 | 4-Amino-5-chloro-2-methoxybenzoic acid | 7206-70-4 | C8H8ClNO3 | 详情 | 详情 |