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【结 构 式】 
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【分子编号】19507 【品名】benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C22H26N2O3 【 分 子 量 】366.46012 【元素组成】C 72.11% H 7.15% N 7.64% O 13.1% |
合成路线1
该中间体在本合成路线中的序号：(XI)L-Picolinic acid (II) is protected with benzyl chloroformiate (VII) to afford compound (VIII), which is condensed with 2-methylaniline (IX) by means SOCl2/DMAP to yield amide (X). This compound (X) is methylated by treatment with palladium acetate (Pd(Oac)2) to obtain compound (XI), which is deprotected by means HBr to yield compound (V). Finally, this compound (V) is alkylated with 1-iodopropane by means potassium carbonate (K2CO3) to yield Ropivacaine.
| 【1】 Sandeberg, R.V. (AstraZeneca plc); S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate, process for its preparation and pharmaceutical preparation containing it. EP 0239710; US 4870086 . |
| 【2】 T. af Ekenstam, B.; Bovin, C. (Alpharma Inc.); L-N-n-Propylpipecolic acid-2,6-xylidide and method for preparing the same. JP 1985502054; WO 8500599 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 | |
| (II) | 17380 | (2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid | 3105-95-1 | C6H11NO2 | 详情 | 详情 |
| (V) | 17531 | (2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide | C14H20N2O | 详情 | 详情 | |
| (VII) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (VIII) | 19504 | (2S)-1-[(benzyloxy)carbonyl]-2-piperidinecarboxylic acid | C14H17NO4 | 详情 | 详情 | |
| (IX) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (X) | 19506 | benzyl (2S)-2-(2-toluidinocarbonyl)-1-piperidinecarboxylate | C21H24N2O3 | 详情 | 详情 | |
| (XI) | 19507 | benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate | C22H26N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)2) The protection of L-pipecolic acid (II) with benzyl chloroformate (VII) gives the benzyloxycarbonyl compound (VIII), which is condensed with o-toluidine (IX) by means of SOCl2 and dimethylaminopyridine (DMAP) yielding the amide (X). The methylation of (X) with methyl iodide and palladium diacetate in acetic acid affords the 2,6-xylidide (XI), which is deprotected with HBr in acetic acid to give L-pipecolic acid 2,6-xylidide (V). Finally, this compound is alkylated with propyl iodide and K2CO3 in acetonitrile.
| 【1】 Prous, J.; Castaner, J.; ROPIVACAINE HYDROCHLORIDE < Rec INNM >. Drugs Fut 1989, 14, 8, 767. |
| 【2】 Sahlberg, C.; Synthesis of carbon-14 labelled ropivacaine, a local anaesthetic agent. J Label Compd Radiopharm 1987, 24, 5, 529. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 17380 | (2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid | 3105-95-1 | C6H11NO2 | 详情 | 详情 |
| (V) | 17531 | (2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide | C14H20N2O | 详情 | 详情 | |
| (VI) | 19502 | Propyl bromide; 1-Bromopropane | 106-94-5 | C3H7Br | 详情 | 详情 |
| (VII) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (VIII) | 19504 | (2S)-1-[(benzyloxy)carbonyl]-2-piperidinecarboxylic acid | C14H17NO4 | 详情 | 详情 | |
| (IX) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (X) | 19506 | benzyl (2S)-2-(2-toluidinocarbonyl)-1-piperidinecarboxylate | C21H24N2O3 | 详情 | 详情 | |
| (XI) | 19507 | benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate | C22H26N2O3 | 详情 | 详情 |