【结 构 式】 |
【分子编号】36449 【品名】6-(benzyloxy)-7-methyl-1,3-benzodioxole-5-carbaldehyde 【CA登记号】 |
【 分 子 式 】C16H14O4 【 分 子 量 】270.28476 【元素组成】C 71.1% H 5.22% O 23.68% |
合成路线1
该中间体在本合成路线中的序号:(I)The condensation of benzaldehyde (I) with malonic ester (II) by means of piperidine and acetic acid in benzene gives the unsaturated malonate (III), which by a selective ester cleavage and a Curtius rearrangement by means of N3-PO(OPh)2 and Et3N in toluene yields the unsaturated aminoester (IV). The reduction of (IV) with a chiral rhodium catalyst affords the chiral protected aminoester (V), which is cyclized to the bridged lactone (VI) by means of BF3 ethearate in dichloromethane. Reductive cleavage of the benzyloxycarbonyl benzyl ether groups of (VI) with H2 over Pd/C affords the free aminophenol (VII). The condensation of (VII) with aldehyde (VIII) (obtained by reduction of ester (IX) with DIBAL in dichloromethane) by means of KCN and AcOH, and after allylation of the aromatic OH group with allyl bromide, the intermediate (X) is obtained. The reduction of the lactone group of (X) with DIBAL, followed by desilylation with KF and cyclization with CH3SO3H affords the polycyclic compound (XI).
【1】 Gin, D.Y.; Corey, E.J.; Kania, R.S.; Enantioselective total synthesis of Ecteinascidin 743. J Am Chem Soc 1996, 118, 38, 9202-03. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 | |
(I) | 36449 | 6-(benzyloxy)-7-methyl-1,3-benzodioxole-5-carbaldehyde | C16H14O4 | 详情 | 详情 | |
(II) | 36450 | 1-(2,2-dimethoxyethyl) 3-isobutyl malonate | C10H16O6 | 详情 | 详情 | |
(III) | 36451 | 1-(2,2-dimethoxyethyl) 3-isobutyl 2-[(E)-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-5-yl]methylidene]malonate | C26H28O9 | 详情 | 详情 | |
(IV) | 36452 | 2,2-dimethoxyethyl (Z)-2-[[(benzyloxy)carbonyl]amino]-3-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-5-yl]-2-propenoate | C30H31NO9 | 详情 | 详情 | |
(V) | 36453 | 2,2-dimethoxyethyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-5-yl]propanoate | C30H33NO9 | 详情 | 详情 | |
(VI) | 35454 | 2-phenyl-1H-imidazole-4-carbaldehyde | C10H8N2O | 详情 | 详情 | |
(VII) | 36455 | (1R,12S)-9-hydroxy-8-methyl-4,6,14-trioxa-16-azatetracyclo[10.3.1.0(2,10).0(3,7)]hexadeca-2,7,9-trien-13-one | C13H13NO5 | 详情 | 详情 | |
(VIII) | 36456 | allyl (1S)-1-(3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzyl)-2-oxoethylcarbamate | C26H45NO6Si2 | 详情 | 详情 | |
(IX) | 36457 | methyl (2S)-2-[[(allyloxy)carbonyl]amino]-3-(3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methoxyphenyl)propanoate | C27H47NO7Si2 | 详情 | 详情 | |
(X) | 36458 | allyl (1S,2R)-2-[(1R,12S)-9-(allyloxy)-8-methyl-13-oxo-4,6,14-trioxa-16-azatetracyclo[10.3.1.0(2,10).0(3,7)]hexadeca-2,7,9-trien-16-yl]-1-(3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzyl)-2-cyanoethylcarbamate | C43H61N3O10Si2 | 详情 | 详情 | |
(XI) | 36459 | allyl (1R,2S,13R,15R,16S)-5-(allyloxy)-15-cyano-20,22-dihydroxy-13-(hydroxymethyl)-21-methoxy-6-methyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-24-carboxylate | C31H33N3O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)6-(Benzyloxy)-7-methyl-1,3-benzodioxole-5-carbaldehyde (scheme 13922101a, cp. (I)). The protection of the OH group of phenol (XXIV) with Mom-Br and NaH in DMF/ethyl ether gives the methoxymethyl ether (XXV), which is methylated with MeI and BuLi in hexane yielding the 4-methyl derivative (XXVI). The formylation of (XXVI) with n-BuLi and DMF in THF affords the carbaldehyde (XXVII), which is deprotected with MsOH in dichloromethane giving 6-hydroxy-7-methyl-1,3-benzodioxole-5-carbaldehyde (XXVIII). Finally, this compound is benzylated with benzyl bromide and NaH in DMF providing the desired intermediate (I).
【1】 Gin, D.Y.; Corey, E.J.; Kania, R.S.; Enantioselective total synthesis of Ecteinascidin 743. J Am Chem Soc 1996, 118, 38, 9202-03. |
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) | 36449 | 6-(benzyloxy)-7-methyl-1,3-benzodioxole-5-carbaldehyde | C16H14O4 | 详情 | 详情 | |
(XXIV) | 10985 | 1,3-Benzodioxol-5-ol; Sesamol | 533-31-3 | C7H6O3 | 详情 | 详情 |
(XXV) | 38101 | 1,3-benzodioxol-5-yl methoxymethyl ether; 5-(methoxymethoxy)-1,3-benzodioxole | C9H10O4 | 详情 | 详情 | |
(XXVI) | 38102 | 5-(methoxymethoxy)-4-methyl-1,3-benzodioxole; methoxymethyl 4-methyl-1,3-benzodioxol-5-yl ether | C10H12O4 | 详情 | 详情 | |
(XXVII) | 38103 | 6-(methoxymethoxy)-7-methyl-1,3-benzodioxole-5-carbaldehyde | C11H12O5 | 详情 | 详情 | |
(XXVIII) | 38104 | 6-hydroxy-7-methyl-1,3-benzodioxole-5-carbaldehyde | C9H8O4 | 详情 | 详情 |