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【结 构 式】 
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【分子编号】15214 【品名】(2S)-2-[(4-methylphenoxy)methyl]-2,3-dihydro-1,4-benzodioxine; (2S)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylphenyl ether 【CA登记号】 |
【 分 子 式 】C16H16O3 【 分 子 量 】256.30124 【元素组成】C 74.98% H 6.29% O 18.73% |
合成路线1
该中间体在本合成路线中的序号：(VIII)A new synthesis of MKC-242 has been described: The tosylation of 2,2-dimethyl-1,3-dioxolane-4(R)-methanol (I) with tosyl chloride in pyridine gives the expected tosylate (II), which is condensed with pyrocatechol monobenzyl ether (III) by means of NaH in N-methylpyrrolidone (NMP) yielding 4(S)-(2-benzyloxyphenoxymethyl)-2,2-dimethyl-1,3-dioxolane (IV). The hydrolysis of the dioxolane ring with hot acetic acid affords the diol (V), which is tosylated with tosyl chloride, triethylamine and dimethylaminopyridine (DMAP) in dichloromethane to give the ditosylate (VI). The debenzylation of (VI) with H2 over Pd/C in methanol/ethyl acetate yields the phenol (VII), which is cyclized by means of K2CO3 in NMP affording 2(R)-(tosyloxymethyl)-1,4-benzodioxane (VIII). Finally, this compound is condensed with 3-(1,3-benzodioxol-5-yloxy)propylamine (IX) by means of ethyl diisopropylamine in NMP. The amine (IX) used as second starting compound has been obtained as follows: The condensation of N-(3-bromopropyl)phthalimide (X) with 5-hydroxy-1,3-benzodioxole (XI) by means of NaH in hot NMP gives N-[3-(1,3-benzodioxol-5-yloxy)propyl]phthalimide (XII), which is then treated with hydrazine in refluxing methanol to obtain amine (IX).
| 【1】 Sugano, M.; Saito, K.; Yamabe, H.; Chaki, H.; Abe, M.; Tabata, R.; Synthesis and 5-HT1A affinity of an optically active benzodioxane derivative MKC-242; a novel anxiolytic and antidepressant agent. 214th ACS Natl Meet (Sept. 7-11, Las Vegas) 1997, Abst MEDI 019. |
| 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) | 12698 | [(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methanol | 14347-78-5 | C6H12O3 | 详情 | 详情 |
| (II) | 15208 | (S)-(+)-2,2-Dimethyl-4-(hydroxymethyl)-1,3-dioxolane-p-toluenesulfonate; [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate | 23735-43-5 | C13H18O5S | 详情 | 详情 |
| (III) | 15209 | Phenol, 2-(phenylmethoxy)-; 2-(benzyloxy)phenol | 6272-38-4 | C13H12O2 | 详情 | 详情 |
| (IV) | 15210 | benzyl 2-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl ether; (4R)-4-[[2-(benzyloxy)phenoxy]methyl]-2,2-dimethyl-1,3-dioxolane | C19H22O4 | 详情 | 详情 | |
| (V) | 15211 | (2S)-3-[2-(benzyloxy)phenoxy]-1,2-propanediol | C16H18O4 | 详情 | 详情 | |
| (VI) | 15212 | (1S)-2-[2-(benzyloxy)phenoxy]-1-[(4-methylphenoxy)methyl]ethyl 4-methylbenzenesulfonate | C30H30O6S | 详情 | 详情 | |
| (VII) | 15213 | (1S)-2-(2-hydroxyphenoxy)-1-[(4-methylphenoxy)methyl]ethyl 4-methylbenzenesulfonate | C23H24O6S | 详情 | 详情 | |
| (VIII) | 15214 | (2S)-2-[(4-methylphenoxy)methyl]-2,3-dihydro-1,4-benzodioxine; (2S)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylphenyl ether | C16H16O3 | 详情 | 详情 | |
| (IX) | 15206 | 3-(1,3-benzodioxol-5-yloxy)-1-propanamine; 3-(1,3-benzodioxol-5-yloxy)propylamine | C10H13NO3 | 详情 | 详情 | |
| (X) | 15216 | N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione | 5460-29-7 | C11H10BrNO2 | 详情 | 详情 |
| (XI) | 10985 | 1,3-Benzodioxol-5-ol; Sesamol | 533-31-3 | C7H6O3 | 详情 | 详情 |
| (XII) | 15218 | 2-[3-(1,3-benzodioxol-5-yloxy)propyl]-1H-isoindole-1,3(2H)-dione | C18H15NO5 | 详情 | 详情 |